European Journal of Pharmacology
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Halichlorine is a novel L-type Ca(2+) channel inhibitor isolated from the marine sponge Halichondria okadai Kadota.
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Halichlorine, isolated from a marine sponge Halichondria okadai Kadota, has an unique structure and it's physiological activity virtually unknown. In the present study, we investigated the direct effect of halichlorine on vascular contractility. In endothelium-denuded rat aorta, while the treatment of halichlorine (0.01-10muM) didn't induce vascular contraction, halichlorine (0.01-10muM) dose-dependently inhibited both the steady state precontractions induced by high K(+) (65.4mM) and phenylephrine (1muM). The vasodilator effect of halichlorine (10muM) on high K(+) (65.4mM)-induced contraction was more potent than that...
Source: European Journal of Pharmacology - November 14, 2009 Category: Drugs & Pharmacology Authors: Tsubosaka Y, Murata T, Kinoshita K, Yamada K, Uemura D, Hori M, Ozaki H Tags: Eur J Pharmacol Source Type: journals
Biological activity of EXf, a peptide analogue of exendin-4.Email this article to a colleague.
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Exendin-4 is an incretin mimetic that has been developed for the treatment of patients with type 2 diabetes. And EXf is an available carboxy-terminal truncated fragment of exendin-4 with two amino acid substitutions. The purpose of these studies was to evaluate the biological activity of EXf. After a single subcutaneous injection, EXf significantly decreased plasma glucose concentration and glucose excursion following the administration of an oral glucose challenge both in non-diabetic (ICR), monosodium L-glutamate induced insulin resistance (MSG-IR) and diabetic KK-ay mice. Meanwhile, EXf resulted in an increase of fi...
Source: European Journal of Pharmacology - November 14, 2009 Category: Drugs & Pharmacology Authors: Song GM, Huan Y, Sun SJ, Chen YT, Liu Q, Shen ZF Tags: Eur J Pharmacol Source Type: journals
Mechanisms of action of hydrogen sulfide in relaxation of mouse distal colonic smooth muscle.Email this article to a colleague.
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Hydrogen sulfide (H(2)S) has been suggested as a gaseous neuromodulator in mammals. The aim of this study was to examine the influence of H(2)S on contractility in mouse distal colon. The effect of sodium hydrogen sulfide (NaHS; H(2)S donor) on prostaglandin F(2alpha) (PGF(2alpha))-contracted circular muscle strips of mouse distal colon was investigated. In addition, tension and cytosolic calcium concentration ([Ca(2+)](cyt)) in the mouse distal colon strips were measured simultaneously in the presence of NaHS. NaHS caused concentration-dependent relaxation of the pre-contracted mouse distal colon strips. The NaHS-indu...
Source: European Journal of Pharmacology - November 14, 2009 Category: Drugs & Pharmacology Authors: Dhaese I, Van Colen I, Lefebvre RA Tags: Eur J Pharmacol Source Type: journals
The dopaminergic stabilizers pridopidine (ACR16) and (-)-OSU6162 display dopamine D(2) receptor antagonism and fast receptor dissociation properties.Email this article to a colleague.
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A new pharmacological class of CNS ligands with the unique ability to stimulate or suppress motor and behavioral symptoms depending on the prevailing dopaminergic tone has been suggested as "dopaminergic stabilizers". The molecular mode-of-action of dopaminergic stabilizers is not yet fully understood, but they are assumed to act via normalization of dopaminergic signaling, through interactions with the dopamine D(2) receptor. Here we have evaluated the dopaminergic stabilizers pridopidine (ACR16) and (-)-OSU6162, as well as the new compound N-{[(2S)-5-chloro-7-(methylsulfonyl)-2,3-dihydro-1,4-benzodioxin-2-yl]methyl}e...
Source: European Journal of Pharmacology - November 14, 2009 Category: Drugs & Pharmacology Authors: Dyhring T, Nielsen EO, Sonesson C, Pettersson F, Karlsson J, Svensson P, Christophersen P, Waters N Tags: Eur J Pharmacol Source Type: journals
Curcumin protects rats against acetaminophen-induced hepatorenal damages and shows synergistic activity with N-acetyl cysteine.Email this article to a colleague.
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In this study we investigated the effects of curcumin, derived from plant Curcuma Longa, on acetaminophen toxicity, and the possibility of combining therapy of curcumin and N-acetyl cysteine (NAC) to treat this toxicity. The experiments were conducted on 72 male Sprague-Dawley rats randomly divided into 12 groups. Control group was left without treatment, and the other groups were treated with different combinations of acetaminophen, curcumin and NAC. Fifteen min after intraperitoneal injection, the blood level of curcumin was measured using HPLC. Blood levels of AST (Aspartate Aminotransferase), ALT (Alanine Aminotransfer...
Source: European Journal of Pharmacology - November 14, 2009 Category: Drugs & Pharmacology Authors: Kheradpezhouh E, Panjehshahin MR, Miri R, Javidnia K, Noorafshan A, Monabati A, Dehpour AR Tags: Eur J Pharmacol Source Type: journals
In vitro pharmacological selectivity profile of oseltamivir prodrug (Tamiflu((R))) and active metabolite.Email this article to a colleague.
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In this study, the in vitro selectivity profile of oseltamivir prodrug and active metabolite was investigated. Both compounds lacked clinically relevant pharmacological activities on human, rodent and primate neuraminidases and on a panel of 155 other molecular targets, including those relevant for mood, cognition and behavior. Neuropsychiatric adverse events observed in influenza patients are likely a phenomenon caused by the infection rather than by oseltamivir.
PMID: 19917275 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - November 13, 2009 Category: Drugs & Pharmacology Authors: Lindemann L, Jacobsen H, Schuhbauer D, Knoflach F, Gatti S, Wettstein JG, Loetscher H, Chu T, Ebeling M, Paulson JC, Prinssen E, Brockhaus M Tags: Eur J Pharmacol Source Type: journals
The putative lipid raft modulator miltefosine displays immunomodulatory action in T-cell dependent dermal inflammation models.Email this article to a colleague.
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Miltefosine is currently marketed for treatment of skin metastasis of breast cancer and leishmaniasis. The mechanism of action is not fully understood, however, miltefosine is considered to be a prototype lipid raft modulator. The compound was shown to inhibited anti-IgE induced histamine release from human skin mast cell. After topical treatment it reduced skin reaction in allergic human volunteers undergoing skin prick test. The aim of this study was to test whether miltefosine could also modify T-cell signalling and whether the drug may be useful for the treatment of atopic dermatitis. Miltefosine (20microM) inhibit...
Source: European Journal of Pharmacology - November 13, 2009 Category: Drugs & Pharmacology Authors: Bäumer W, Wlaź P, Jennings G, Rundfeldt C Tags: Eur J Pharmacol Source Type: journals
Anti-glycative effects of oleanolic acid and ursolic acid in kidney of diabetic mice.Email this article to a colleague.
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Inhibitory effects of oleanolic acid (OA) and ursolic acid (UA) on aldose reductase (AR) and glycative products in kidney of diabetic mice were examined. OA or UA at 0.05, 0.1 or 0.2% was supplied for 10weeks. Diabetic mice with 0.1 or 0.2% OA or UA treatments had significantly higher body weight and lower kidney weight at wk 5 and 10 (P<0.05). OA or UA intake at 0.1 or 0.2% increased their content in kidney, dose-dependently decreased plasma glucose, HbA1c, renal N(epsilon)-(carboxymethyl)lysine, urinary glycated albumin and urinary albumin levels; elevated plasma insulin and renal creatinine clearance levels; as w...
Source: European Journal of Pharmacology - November 13, 2009 Category: Drugs & Pharmacology Authors: Wang ZH, Hsu CC, Huang CN, Yin MC Tags: Eur J Pharmacol Source Type: journals
Insulin-releasing and metabolic effects of small molecule GLP-1 receptor agonist 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline.Email this article to a colleague.
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Much recent attention has focused on the GLP-1 receptor as a potential target for antidiabetic drugs. Enzyme resistant GLP-1 mimetics such as exenatide are now employed for the treatment of type 2 diabetes, but must be administered by injection. The present study has examined and compared the in vitro and in vivo metabolic actions of a small molecule GLP-1 receptor agonist 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline (DMB), with native GLP-1, exenatide and liraglutide. DMB significantly stimulated in vitro insulin secretion from BRIN BD11 cells but with decreased molar potency compared to native GLP-1 o...
Source: European Journal of Pharmacology - November 13, 2009 Category: Drugs & Pharmacology Authors: Irwin N, Flatt PR, Patterson S, Green BD Tags: Eur J Pharmacol Source Type: journals
Hypoxia-induced cell damage is reduced by mild hypothermia and postconditioning with catalase in-vitro: Application of an enzyme based oxygen deficiency system.Email this article to a colleague.
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Mild hypothermia and pharmacological postconditioning are widespread therapeutical treatment options that positively influence the clinical outcome after tissue hypoxia. In the study presented, a two-enzyme based in-vitro oxygen deficiency model in combination with cultured HT-1080 fibrosarcoma cells was employed to mimic the in-vivo situation of hypoxia and to evaluate the influence of mild hypothermia and postconditioning with catalase on hypoxia-mediated cell damage. Using the in-vitro oxygen deficiency model, partial pressure of oxygen was rapidly reduced to levels below 5mmHg in the culture media and cells respond...
Source: European Journal of Pharmacology - November 13, 2009 Category: Drugs & Pharmacology Authors: Zitta K, Meybohm P, Bein B, Rodde C, Steinfath M, Scholz J, Albrecht M Tags: Eur J Pharmacol Source Type: journals
Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice.Email this article to a colleague.
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We examined the effects of two-drug combinations of gabapentin, oxcarbazepine, and amitriptyline on nociception in diabetic mice and aimed to determine the type of interaction between components. The nociceptive responses in normal and diabetic mice were assessed by the tail-flick test. The testing was performed before and three weeks after the diabetes induction with streptozotocin (150mg/kg; i.p.), when the antinociceptive effects of gabapentin, oxcarbazepine, amitriptyline and their two-drug combinations were examined. Gabapentin (10-40mg/kg; p.o.) and oxcarbazepine (20-80mg/kg; p.o.) produced a significant, dose-depend...
Source: European Journal of Pharmacology - November 13, 2009 Category: Drugs & Pharmacology Authors: Tomić MA, Vučković SM, Stepanović-Petrović RM, Micov AM, Ugrešić ND, Prostran MS, Bošković B Tags: Eur J Pharmacol Source Type: journals
A noble function of BAY 11-7082: Inhibition of platelet aggregation mediated by an elevated cAMP-induced VASP, and decreased ERK2/JNK1 phosphorylations.Email this article to a colleague.
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In conclusion, BAY 11-7082 inhibits platelet activation, granule secretion, and aggregation, and that this effect is mediated by inhibition of JNK1 and ERK2 phosphorylations, and partially by stimulation of cAMP-dependent PKA VASP phosphorylation. The ability of BAY 11-7082 to inhibit platelet function might be relevant in cases involving aberrant platelet activation where the drug is considered as anti-atherothrombosis, and anti-inflammatory therapy.
PMID: 19913011 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - November 10, 2009 Category: Drugs & Pharmacology Authors: Lee HS, Kim SD, Lee WM, Endale M, Kamruzzaman SM, Oh WJ, Cho JY, Kim SK, Cho HJ, Park HJ, Rhee MH Tags: Eur J Pharmacol Source Type: journals
Topical and systemic administrations of ketanserin attenuate hypersensitivity and expression of CGRP in rats with spinal nerve ligation.Email this article to a colleague.
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This study suggests that 5-HT and 5-HT2A receptors contribute to the maintenance of neuropathic pain by up-regulating the expression of CGRP-IR, and that topical and systemic administrations of ketanserin are promising therapies for relieving neuropathic pain without tolerance.
PMID: 19913012 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - November 10, 2009 Category: Drugs & Pharmacology Authors: Wang D, Gao Y, Ji H, Hong Y Tags: Eur J Pharmacol Source Type: journals
Age-related differences in MK-801 induced behaviors in dopamine D(3) receptor knock out mice.Email this article to a colleague.
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It is not known if age plays an important role in the D3 receptor regulation of N-methyl-D-aspartate (NMDA) receptor antagonist induced hyperactivity. Wild type (WT) and dopamine D(3) receptor mutant (D(3)R KO) mice were divided into Young (under 7 months) and Middle Age (over 12 months) groups and tested for dizocilpine (MK-801)-induced hyperactivity and rearing. Mice were administered vehicle (saline, 1 ml/100 g body weight, i.p.), or dopamine D(3) receptor preferring antagonists 3aR,9bS)-N[4-(8-cyano-1,3a,4,9b-tetrahydro-3H-benzopyrano[3,4-c]pyrrole-2-yl)-butyl] (4-phenyl) benzamide) (S33084, 1.0 mg/kg, i.p.) and 5,...
Source: European Journal of Pharmacology - November 9, 2009 Category: Drugs & Pharmacology Authors: Iarkov AV, Der TC, Joyce JN Tags: Eur J Pharmacol Source Type: journals
Protective roles of Asperosaponin VI, a triterpene saponin isolated from Dipsacus asper Wall on acute myocardial infarction in rats.Email this article to a colleague.
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In this study, we investigated the anti-myocardial ischemia effects of Asperosaponin VI(ASA VI) both in vivo and in vitro. An animal model of myocardial ischemia(MI) injury was induced by coronary occlusion, pretreatment with ASA VI (10 and 20mg/kg, i.v.) could protect the heart from ischemia injury by decreasing the levels of creatine kinase-MB(CK-MB), lactate dehydrogenase(LDH), glutamic oxalacetic transaminase(GOT) and cardiac troponin T(cTnT) in serum, increasing the levels of catalase, glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD) levels in heart, and decreasing that of malondialdehyde(MDA) level in acu...
Source: European Journal of Pharmacology - November 9, 2009 Category: Drugs & Pharmacology Authors: Li C, Liu Z, Tian J, Li G, Jiang W, Zhang G, Chen F, Lin P, Ye Z Tags: Eur J Pharmacol Source Type: journals
Neferine, a bisbenzylisoquinline alkaloid attenuates bleomycin-induced pulmonary fibrosis.Email this article to a colleague.
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In this study, we evaluated the potential anti-fibrotic property of neferine, a bisbenzylisoquinline alkaloid extracted from the seed embryo of Nelumbo mucifera Gaertn. Intratracheal bleomycin administration resulted in pulmonary fibrosis 14 and 21days posttreatment, as evidenced by increased hydroxyproline content in bleomycin group (255.77+/-97.17microg/lung and 269.74+/-40.92microg/lung) compared to sham group (170.78+/-76.46microg/lung and 191.24+/-60.45microg/lung), and the hydroxyproline was significantly suppressed (193.07+/-39.55microg/lung and 201.08+/-71.74microg/lung) by neferine administration (20mg/kg, b.i.d)....
Source: European Journal of Pharmacology - November 9, 2009 Category: Drugs & Pharmacology Authors: Zhao L, Wang X, Chang Q, Xu J, Huang Y, Guo Q, Zhang S, Wang W, Chen X, Wang J Tags: Eur J Pharmacol Source Type: journals
Block effect of capsaicin on hERG potassium currents was enhanced by S6 mutation at Y652.Email this article to a colleague.
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In conclusion, capsaicin blocks hERG channels by binding to both the closed and open channel states.Y652 was important as a molecular determinant of blockade. Mutation Y652A enhances the drug block, which may cause some patients to be particularly sensitive to capsaicin clinically.
PMID: 19903464 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - November 7, 2009 Category: Drugs & Pharmacology Authors: Xing J, Ma J, Zhang P, Fan X Tags: Eur J Pharmacol Source Type: journals
Decreased number of caveolae in endothelial cells impairs the relaxation induced by acetylcholine in hypertensive rat aortas.Email this article to a colleague.
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The present study was designed to investigate the contribution of endothelial cells caveolae to vascular relaxation in aortas from normotensive (2K) and renal hypertensive (2K-1C) rat. For that purpose, concentration-effect curves to acetylcholine were constructed in 2K and 2K-1C intact endothelium aortic rings, in the absence or in the presence of the caveolae disassembler methyl-beta-ciclodextrin. The potency (pD(2)) and the maximum relaxant effect to acetylcholine were greater in 2K than in 2K-1C aortas. Methyl-beta-ciclodextrin reduced the pD(2) in 2K and maximum relaxant effect in both 2K and 2K-1C. The quantifica...
Source: European Journal of Pharmacology - November 7, 2009 Category: Drugs & Pharmacology Authors: Rodrigues GJ, Restini CB, Lunardi CN, Dos Anjos Neto M, Moreira JE, Bendhack LM Tags: Eur J Pharmacol Source Type: journals
Lack of beneficial metabolic effects of quercetin in adult spontaneously hypertensive rats.Email this article to a colleague.
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In conclusion, quercetin reduced blood pressure, left ventricular and renal hypertrophy and improved NO-dependent acetylcholine relaxation. However, and despite its antioxidant effects, quercetin was unable to improve insulin sensitivity possibly through its specific interference with the insulin signalling pathway.
PMID: 19903466 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - November 7, 2009 Category: Drugs & Pharmacology Authors: Romero M, Jiménez R, Hurtado B, Moreno JM, Rodríguez-Gómez I, López-Sepúlveda R, Zarzuelo A, Pérez-Vizcaino F, Tamargo J, Vargas F, Duarte J Tags: Eur J Pharmacol Source Type: journals
Biomechanical and histological outcome of combined raloxifene-estrogen therapy on skeletal and reproductive tissues.Email this article to a colleague.
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Estrogen replacement is a potent therapy for postmenopausal osteoporosis. However, its carcinogenic effects on breasts and the uterus limit its utilization. Raloxifene has estrogen-like effects on bones without the carcinogenic symptoms on breast or uterine tissue. Their individual effects are well characterized, but the results of their interaction remains elusive. In this work, we investigate the consequences of a combined raloxifene/estrogen therapy on bone and uterus with experimental osteoporosis. 40 Wistar rats began treatment 3months post ovariectomy. Estrogen and raloxifene were administered 0.03mg/kg/day and 1...
Source: European Journal of Pharmacology - November 7, 2009 Category: Drugs & Pharmacology Authors: Tasci A, Bilgili H, Altunay H, Gecit MR, Keskin D Tags: Eur J Pharmacol Source Type: journals
Protein kinase C is inhibited by bisphosphonates in prostate cancer PC-3 cells.Email this article to a colleague.
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Bisphosphonates are expected to be effective at preventing tumor metastasis to bone tissue. Since protein kinase C (PKC) plays a crucial role in cancer progression, we examined the effect of bisphosphonates on PKC expression to clarify the mechanism behind the inhibition of the bone metastasis of prostate cancer by bisphosphonates. We found that pamidronate inhibits PKC protein expression and PKC activity in prostate cancer PC-3 cells. PKC protein expression was markedly reduced by treatment with 100microM of pamidronate. The inhibitory effect of PKC expression by pamidronate was specific for PKCalpha and PKCzeta. Nitr...
Source: European Journal of Pharmacology - November 7, 2009 Category: Drugs & Pharmacology Authors: Tatsuda Y, Iguchi K, Usui S, Suzui M, Hirano K Tags: Eur J Pharmacol Source Type: journals
XIAP-mediated protection of H460 lung cancer cells against cisplatin.Email this article to a colleague.
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Molecular mechanism(s) responsible for drug resistance of non-small cell lung cancer (NSCLC) cells to cisplatin was investigated. Results showed that cisplatin (50muM)-induced cell death (apoptosis) was more significant in CH27 and A549 cell lines than in H460. The high protein levels of X-linked inhibitor-of-apoptosis protein (XIAP) observed in H460 cells appeared to play a key role in the regulation of cisplatin resistance of H460 cells. XIAP can bind to and suppress the activities of caspase 3 in H460 cells and lead to apoptosis inhibition of these cells. Blockade of XIAP activity by Embelin (XIAP inhibitor) or siRN...
Source: European Journal of Pharmacology - November 7, 2009 Category: Drugs & Pharmacology Authors: Cheng YJ, Jiang HS, Hsu SL, Lin LC, Wu CL, Ghanta VK, Hsueh CM Tags: Eur J Pharmacol Source Type: journals
A direct relationship between aggressive behavior in the resident/intruder test and cell oxidative status in adult male mice.Email this article to a colleague.
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The objective of the present study was to examine the relationship between the level of intracellular reactive oxygen species in the peripheral blood granulocytes of mice, as evaluated by 2',7'-dichlorofluorescin diacetate (DCFH-DA), a sensor of reactive oxygen species, and the aggressive behavior of these mice, as estimated by the resident/intruder test. Our results showed a significant, linear and positive relationship (p<0.001) between the intracellular redox status of peripheral blood granulocytes and the aggressive behavior levels of adult male mice (correlation coefficients (R(2)) ranging from 0.75 to 0.77). This ...
Source: European Journal of Pharmacology - November 7, 2009 Category: Drugs & Pharmacology Authors: Rammal H, Bouayed J, Soulimani R Tags: Eur J Pharmacol Source Type: journals
Selective inhibition of MDR1 (ABCB1) by HM30181 increases oral bioavailability and therapeutic efficacy of paclitaxel.Email this article to a colleague.
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In this study, we examined the pharmacologic characteristics of HM30181, a newly developed MDR1 inhibitor, and tested its capacity to increase the oral bioavailability and efficacy of paclitaxel, an anti-cancer drug usually given by intravenous injection. In the ATPase assay using MDR1-enriched vesicles, HM30181 showed the highest potency (IC(50)=0.63nM) among several MDR1 inhibitors, including cycloporin A, XR9576, and GF120918, and effectively blocked transepithelial transport of paclitaxel in MDCK monolayers (IC(50)=35.4nM). The ATPase inhibitory activity of HM30181 was highly selective to MDR1. HM30181 did not inhibit ...
Source: European Journal of Pharmacology - November 7, 2009 Category: Drugs & Pharmacology Authors: Kwak JO, Lee SH, Lee GS, Kim MS, Ahn YG, Lee JH, Kim SW, Kim KH, Lee MG Tags: Eur J Pharmacol Source Type: journals
Characterization of scratching behavior induced by intradermal administration of morphine and fentanyl in mice.Email this article to a colleague.
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In conclusion, opioid induced itching may involve in peripheral opioid receptors. Moreover, histamine and arachidonic acid metabolites played no main role in opioid-induced scratching behavior.
PMID: 19900440 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - November 6, 2009 Category: Drugs & Pharmacology Authors: Yamamoto A, Kuyama S, Kamei C, Sugimoto Y Tags: Eur J Pharmacol Source Type: journals
Locomotor actvitiy induced by MK-801 is enhanced in dopamine D(3) receptor knock out mice but suppression by dopamine D(3)/D(2) antagonists does not occur through the dopamine D(3) receptor.Email this article to a colleague.
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There are contradictory data regarding the role of the dopamine D(3) receptor in regulating N-methyl-D-aspartate (NMDA) receptor antagonist (e.g., dizocilpine) induced hyperactivity. The purpose of the present study was to examine the interaction of dopamine D(3) receptor preferring antagonists U99194A (5,6-dimethoxy-2(dipropylamino)indan) and S33804 ((3aR,9bS)-N[4-(8-cyano-1,3a,4,9b-tetrahydro-3H-benzopyrano[3,4-c]pyrrole-2-yl)-butyl] (4-phenyl)benzamide)) with dizocilpine (MK-801)-induced hyperactivity in wild type (WT) and dopamine D(3) receptor mutant (D(3)R KO) mice. D(3)R KO and WT mice were administered vehicle ...
Source: European Journal of Pharmacology - November 6, 2009 Category: Drugs & Pharmacology Authors: Larkov AV, Der TC, Joyce JN Tags: Eur J Pharmacol Source Type: journals
The role of superoxide anion in the inhibitory effect of SIN-1 in thrombin-activated human platelet adhesion.Email this article to a colleague.
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Reactive oxygen species have an important role in the control of platelet activity. Superoxide anion (O(2)(-)) is a free radical that can be converted into other reactive oxygen species such as peroxynitrite (ONOO(-)) that is formed from the reaction between O(2)(-) and nitric oxide (NO). There are conflicting data on ONOO(-) effects in platelets because it presents pro- or anti-aggregatory actions. 3-morpholinosydnonimine (SIN-1) co-generates NO and O(2)(-), yielding ONOO(-). Therefore, the present study aimed to investigate the mechanisms involved in the inhibition of human platelet adhesion by SIN-1. Microtiter plat...
Source: European Journal of Pharmacology - November 3, 2009 Category: Drugs & Pharmacology Authors: Cardoso MH, Morganti RP, Lilla S, Murad F, De Nucci G, Antunes E, Marcondes S Tags: Eur J Pharmacol Source Type: journals
XLF-III-43, a novel coumarin-aspirin compound, prevents diabetic nephropathy in rats via inhibiting advanced glycation end products.Email this article to a colleague.
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Advanced glycation end products (AGE) have been implicated in the pathogenesis of diabetic complications. The purpose of this study was to examine the novel coumarin-aspirin compound XLF-III-43 in the inhibition of AGE formation in diabetic nephropathy. In vitro analysis showed XLF-III-43 in a dose-dependent manner decreased glucose induced formation of glycation adducts on albumin and inhibited AGE- lysozyme crosslinking. The streptozotocin-induced diabetic rats were used to investigate the beneficial effects of XLF-III-43 treatment on diabetic nephropathy. Administration of XLF-III-43 significantly decreased (P<0....
Source: European Journal of Pharmacology - November 3, 2009 Category: Drugs & Pharmacology Authors: Li H, Zheng X, Wang H, Zhang Y, Xin H, Chen X Tags: Eur J Pharmacol Source Type: journals
Effect of microinjection of histamine into the dorsal hippocampus on the orofacial formalin-induced pain in rats.Email this article to a colleague.
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Brain neuronal histamine, through its receptors, is involved in the central pain perception. In the present study, the effect of microinjection of histamine, mepyramine (a histamine H(1) receptor antagonist) and ranitidine (a histamine H(2) receptor antagonist) into the dorsal hippocampus were investigated on a model of orofacial pain in rats. Orofacial pain was induced by subcutaneous injection of formalin (1%, 50microl) in the upper lip in rats, and the time spent of face rubbing was measured in 3-min blocks for 45min. Formalin induced a marked biphasic (first phase: 0-3min; second phase: 15-33min) pain. Intra-hippoc...
Source: European Journal of Pharmacology - November 2, 2009 Category: Drugs & Pharmacology Authors: Erfanparast A, Tamaddonfard E, Farshid AA, Khalilzadeh E Tags: Eur J Pharmacol Source Type: journals
Protective effect of nicotine on oxidative and cell damage in rats with depression induced by olfactory bulbectomy.Email this article to a colleague.
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In conclusions: i) OBX induces oxidative stress and cell death by apoptosis; and ii) nicotine presents antidepressant and antioxidant effect. All these findings suggest that nicotine would be a therapeutic tool for depression, although more studies are needed in this area to define the appropriate treatment regime.
PMID: 19887066 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - October 31, 2009 Category: Drugs & Pharmacology Authors: Túnez I, Drucker-Colín R, Montilla P, Peña J, Jimena I, Medina FJ, Tasset I Tags: Eur J Pharmacol Source Type: journals
Oral administration of the NAALADase inhibitor GPI-5693 attenuates cocaine-induced reinstatement of drug-seeking behavior in rats.Email this article to a colleague.
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We have recently reported that the endogenous mGlu2/3 agonist N-acetylaspartylglutamate (NAAG) and the N-acetylated-alpha-linked-acidic dipepetidase (NAALADase, a NAAG degradation enzyme) inhibitor 2-PMPA significantly inhibit cocaine self-administration and cocaine-induced reinstatement of drug-seeking behavior by attenuating cocaine-enhanced extracellular dopamine and glutamate in the nucleus accumbens. However, the poor oral bioavailability of NAAG and 2-PMPA limits their practical use in humans. In the present study, we investigated the effects of the orally active NAALADase inhibitor GPI-5693 and its enantiomers o...
Source: European Journal of Pharmacology - October 31, 2009 Category: Drugs & Pharmacology Authors: Peng XQ, Li J, Gardner EL, Ashby CR, Xi ZX Tags: Eur J Pharmacol Source Type: journals
Rosuvastatin inhibits norepinephrine-induced cardiac hypertrophy via suppression of G(h).Email this article to a colleague.
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Statins have recently been shown to produce anti-cardiac hypertrophic effects via the regulation of small GTPases. However, the effects of statins on G protein-mediated cardiac hypertrophy, which is the main pathway of cardiac hypertrophy, have not yet been studied. We sought to evaluate whether statin treatment directly suppresses cardiac hypertrophy through a large G protein-coupled pathway regardless of the regulation of small GTPases. Using neonatal rat cardiomyocytes, we evaluated norepinephrine-induced cardiac hypertrophy for suppressibility of rosuvastatin and the pathways involved by analyzing total protein/DNA...
Source: European Journal of Pharmacology - October 30, 2009 Category: Drugs & Pharmacology Authors: Choi EY, Chang W, Lim S, Song BW, Cha MJ, Kim HJ, Choi E, Jang Y, Chung N, Hwang KC Tags: Eur J Pharmacol Source Type: journals
Evidence for the involvement of matrix metalloproteinases in the cardiovascular effects produced by nicotine.Email this article to a colleague.
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We examined whether nicotine induces the release of MMP-2 and MMP-9 by rat smooth muscle cells (SMC), and whether doxycycline (non-selective MMP inhibitor) inhibits the vascular effects produced by nicotine. SMC were incubated with nicotine 0, 50, and 150 nM for 48h. MMP-2 and MMP-9 levels in the cells supernatants were determined by gelatin zymography. The acute changes in mean arterial pressure caused by nicotine 2mumol/kg (or saline) were assessed in rats pretreated with doxycycline (or saline). We also examined whether doxcycline (30mg/Kg, i.p., daily) modifies the effects of nicotine (10mg/kg/day; 4weeks) on the endot...
Source: European Journal of Pharmacology - October 29, 2009 Category: Drugs & Pharmacology Authors: Jacob-Ferreira AL, Palei AC, Cau SB, Moreno H, Martinez ML, Izidoro-Toledo TC, Gerlach RF, Tanus-Santos JE Tags: Eur J Pharmacol Source Type: journals
The cyclooxygenase-2-selective inhibitor, etodolac, but not aspirin reduces neovascularization in a murine ischemic hind limb model.Email this article to a colleague.
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In conclusion, cyclooxygenase-2 inhibition reduces ischemia-induced neovascularization.
PMID: 19879866 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - October 29, 2009 Category: Drugs & Pharmacology Authors: Tanaka K, Yamamoto Y, Tsujimoto S, Uozumi N, Kita Y, Yoshida A, Shimizu T, Hisatome I Tags: Eur J Pharmacol Source Type: journals
In vitro and in vivo comparison of two non-peptide tachykinin NK(3) receptor antagonists: improvements in efficacy achieved through enhanced brain penetration or altered pharmacological characteristics.Email this article to a colleague.
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Clinical evaluation of tachykinin NK(3) receptor antagonists has provided support for the therapeutic utility of this target in schizophrenia. However, these studies have not been entirely conclusive, possibly because of the pharmacokinetic limitations of these molecules. In the search for tachykinin NK(3) receptor antagonists with improved properties, we have discovered GSK172981 and GSK256471. Both compounds demonstrated high affinity for recombinant human (pKi values 7.7 & 8.9, respectively) and native guinea pig (pKi values 7.8 & 8.4, respectively) tachykinin NK3 receptors. In vitro functional evaluations r...
Source: European Journal of Pharmacology - October 29, 2009 Category: Drugs & Pharmacology Authors: Dawson LA, Langmead CJ, Dada A, Watson JM, Wu Z, de la Flor R, Jones GA, Cluderay JE, Southam E, Murkitt GS, Hill MD, Jones DN, Davies CH, Hagan JJ, Smith PW Tags: Eur J Pharmacol Source Type: journals
The vanilloid receptor TRPV1: Role in cardiovascular and gastrointestinal protection.Email this article to a colleague.
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It has been shown that the transient receptor potential channel vanilloid type 1 (TRPV1) is able to sense a vast range of stimuli and exerts multiple functions under physiological or pathophysiological conditions. TRPV1 not only plays a fundamental role in pain signaling but also involves in many other physiological or pathophysiological functions including the beneficial effects on cardiovascular and gastrointestinal function. It has been found that TRPV1 could be activated by endogenous ligands such as anandamide, N-arachidonoyl dopamine and noleoyldopamine or by exogenous agonists such as capsaicin and rutaecarpine....
Source: European Journal of Pharmacology - October 29, 2009 Category: Drugs & Pharmacology Authors: Peng J, Li YJ Tags: Eur J Pharmacol Source Type: journals
Methanandamide blocks amphetamine-induced behavioral sensitization in rats.Email this article to a colleague.
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Methanandamide acts at targets which modulate amphetamine-induced behaviors. Therefore, we investigated methanandamide effects on the acute hyperactivity produced by a single injection of amphetamine and behavioral sensitization induced by repeated amphetamine exposure in rats. Methanandamide (5mg/kg, i.p.) did not affect basal locomotor or stereotypical activity. Methanandamide (5mg/kg, i.p.) pretreatment did not alter the acute increase in locomotor or stereotypical activities produced by acute amphetamine (2mg/kg, i.p.). For chronic studies, rats injected with amphetamine (2mg/kg, i.p.) once daily for 3 consecutive ...
Source: European Journal of Pharmacology - October 29, 2009 Category: Drugs & Pharmacology Authors: Rasmussen BA, Unterwald EM, Rawls SM Tags: Eur J Pharmacol Source Type: journals
Acanthopanax senticosides B ameliorates oxidative damage induced by hydrogen peroxide in cultured neonatal rat cardiomyocytes.Email this article to a colleague.
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In this study, we investigated the effect of Acanthopanax senticosides B on oxidative damage induced by hydrogen peroxide (H(2)O(2)) of cardiomyocytes. As revealed from the results, when the cardiomyocytes were exposed to H(2)O(2) for designed time and concentration, the percentage of survival cells was down significantly, the activity of lactate dehydrogenase (LDH) and the content of cellular malondialdehyde (MDA) were increased markedly. These results indicated that the cells were subjected to oxidative damage. Treatment with Acanthopanax senticosides B prior to H(2)O(2) (100muM) exposure can increased cell viability sig...
Source: European Journal of Pharmacology - October 29, 2009 Category: Drugs & Pharmacology Authors: Liang Q, Sui D Tags: Eur J Pharmacol Source Type: journals
C-terminal deletion of metabotropic glutamate receptor 1 selectively abolishes coupling to Galphaq.Email this article to a colleague.
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Recent studies indicate that the intracellular C-terminus of Group I metabotropic glutamate receptors (mGlu(1) and mGlu(5) receptor) is important in G protein coupling. To determine the necessity of the C-tail, a deletion mutant of mGlu(1) receptor was constructed, which included the first 841 amino acids of the rat mGlu(1a) receptor (mGlu(1)-dCT). G protein coupling of the receptors was assessed by measuring glutamate mediated inhibition of native calcium currents when each receptor was expressed in isolated sympathetic neurons from the rat superior cervical ganglion. Wild type mGlu(1) receptor activates both the Galp...
Source: European Journal of Pharmacology - October 29, 2009 Category: Drugs & Pharmacology Authors: Kammermeier PJ Tags: Eur J Pharmacol Source Type: journals
Phenylephrine produces late pharmacological preconditioning in the isolated rat heart.Email this article to a colleague.
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In this study, phenylephrine as a selective alpha(1)-adrenoceptor agonist and 5HD (5-hydroxydecanoate) as a putatively specific blocker of the mitochondrial K(ATP) channels were used. Rats were randomly divided into six groups (n=6): (I) Control: surgical procedure was performed with no ischemia/reperfusion, (II) ischemia/reperfusion: hearts underwent regional ischemia/reperfusion, (III) phenylephrine-early preconditioning: phenylephrine (50microM) was perfused for 5min prior to ischemia/reperfusion, (IV) phenylephrine-late preconditioning: rats were treated with phenylephrine (10mg/kg, i.p) 24h prior to ischemia/reperfusi...
Source: European Journal of Pharmacology - October 29, 2009 Category: Drugs & Pharmacology Authors: Naderi R, Imani A, Faghihi M Tags: Eur J Pharmacol Source Type: journals
A novel Podophyllotoxin derivative (YB-1EPN) induces apoptosis and down-regulates express of P-gp in multidrug resistance cell line KBV200.Email this article to a colleague.
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Our group synthesized a new potent antitumor podophyllotoxin derivative, YB-1EPN. In our study, we found that it was more potent than etoposide (VP-16). Interestingly, we found that the KBV200 cell line and K562/A02 cell line were rendered resistant towards VP-16 but not towards YB-1EPN. In vitro, both the cytotoxicity of YB-1EPN and its ability to inhibit KBV200 and K562/A02 cells were determined by MTT assay and growth curve. The IC(50) value of YB-1EPN on KBV200 cell was (2.52+/-0.28) microM in contrast to VP-16(10.1+/-0.220) microM. And YB-1EPN showed a dose-dependent and broad-spectrum antiproliferative activity. ...
Source: European Journal of Pharmacology - October 29, 2009 Category: Drugs & Pharmacology Authors: Chen H, Bi W, Cao B, Yang Z, Chen S, Shang H, Yu P, Yang J Tags: Eur J Pharmacol Source Type: journals
Transient receptor potential vanilloid 1 agonists as candidates for anti-inflammatory and immunomodulatory agents.Email this article to a colleague.
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We recently demonstrated that SA13353 [1-[2-(1-adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea], a novel transient receptor potential vanilloid 1 (TRPV1) agonist, inhibits TNF-alpha production through the activation of capsaicin-sensitive afferent neurons. In the present study, we investigated the effects of SA13353 on lipopolysaccharide (LPS)-induced cytokine production and a murine model of experimental autoimmune encephalomyelitis (EAE). SA13353 inhibited LPS-induced TNF-alpha and interleukin (IL)-1beta production while augmenting IL-10 production in mice. It also inhibited TNF-alpha and IL-1beta mRNA expressi...
Source: European Journal of Pharmacology - October 28, 2009 Category: Drugs & Pharmacology Authors: Tsuji F, Murai M, Oki K, Seki I, Ueda K, Inoue H, Nagelkerken L, Sasano M, Aono H Tags: Eur J Pharmacol Source Type: journals
Effects of bradykinin B(2) receptor stimulation at submucosal ganglia from rat distal colon.Email this article to a colleague.
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Bradykinin acts as an inflammatory mediator in the gut. In the present study we characterized bradykinin-induced changes in the intracellular calcium concentration ([Ca(2+)](i)) in whole-mount submucosal preparations from rat distal colon and examined the bradykinin receptors and subsequent signalling cascades involved. Bradykinin (2.10(-10)-2.10(-7)mol/l) evoked a concentration-dependent increase in [Ca(2+)](i) in about 90% of the investigated neurones. This Ca(2+) response was abolished by the bradykinin B(2) receptor antagonist HOE 140. The B(2) receptor agonist [Hyp(3)]-bradykinin mimicked the kinin response. In co...
Source: European Journal of Pharmacology - October 28, 2009 Category: Drugs & Pharmacology Authors: Avemary J, Diener M Tags: Eur J Pharmacol Source Type: journals
Effects of imipramine or GABA(B) receptor ligands on the immobility, swimming and climbing in the forced swim test in rats following discontinuation of cocaine self-administration.Email this article to a colleague.
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We tested if discontinuation of cocaine self-administration can lead to the development of depressive-like symptoms in the forced swim test expressed as changes in immobility, swimming and climbing behaviors in rats. A "yoked" procedure in which rats were run simultaneously in groups of three, with two rats received the passive injection of cocaine or saline, was employed. Later, we examined whether acute treatment with the classical antidepressant imipramine or GABA(B) receptor ligands could alter the increases in immobility recorded after discontinuation of self-administered cocaine. We found a significant increase (...
Source: European Journal of Pharmacology - October 28, 2009 Category: Drugs & Pharmacology Authors: Frankowska M, Gołda A, Wydra K, Gruca P, Papp M, Filip M Tags: Eur J Pharmacol Source Type: journals
Angiotensin II inhibits activity of human organic anion transporter 3 through activation of protein kinase Calpha: Accelerating endocytosis of the transporter.Email this article to a colleague.
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Human organic anion transporter 3 (hOAT3) belongs to a family of organic anion transporters that play critical roles in the body disposition of numerous clinically important drugs. In the kidney, hOAT3 functions through a tertiary transport mechanism involving two other membrane proteins Na/K-ATPase and Na-dicarboxylate cotransporter. In the current study, we established COS-7 cells stably expressing hOAT3 and examined the regulation of hOAT3 by protein kinase C (PKC) and angiotensin II. Both PKC activation and angiotensin II inhibited hOAT3 transport activity. Angiotensin II induced inhibition of hOAT3 activity could ...
Source: European Journal of Pharmacology - October 28, 2009 Category: Drugs & Pharmacology Authors: Duan P, Li S, You G Tags: Eur J Pharmacol Source Type: journals
Contractile actions of L-type Ca(2+)-agonists in human vas deferens and effects of structurally different Ca(2+)-antagonists.Email this article to a colleague.
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The actions of L-type Ca(2+) agonists, FPL 64176 and Bay K 8644 were investigated in human vas deferens in the presence of structurally different L-type Ca(2+) antagonists. The L-type Ca(2+) agonists (</=3microM, ~10min) produced no detectable contractions but higher concentrations evoked intermittent rhythmic contractility of longitudinal and circular muscles. Exposure to the drugs (1microM,>/=20min) evoked only rhythmic contractility even in moderately depolarizing ([K(+)](O), 10mM) medium. These findings suggest low basal activity of L-type Ca(2+) channels (VOCs) in both muscle types. In the presence of L-type...
Source: European Journal of Pharmacology - October 27, 2009 Category: Drugs & Pharmacology Authors: Amobi N, Guillebaud J, Smith IC Tags: Eur J Pharmacol Source Type: journals
Enhancement effects of nicotine on neurogenic relaxation responses in the corpus cavernosum in rabbits: The role of nicotinic acetylcholine receptor subtypes.Email this article to a colleague.
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Nicotine acts as an agonist of nicotinic acetylcholine receptors, which belong to a superfamily of neurotransmitter-gated ion channels. We previously demonstrated that nicotine increases the electrical field stimulation (EFS)-evoked nitrergic relaxation responses via activation of nicotinic acetylcholine receptors. The aim of the present study is to investigate the subtypes of nicotinic acetylcholine receptors in rabbit corpus cavernosum. EFS-evoked relaxation responses were recorded from corpus cavernosum strips obtained from rabbits with an isometric force displacement transducers. Effects of nicotine on EFS-evoked r...
Source: European Journal of Pharmacology - October 27, 2009 Category: Drugs & Pharmacology Authors: Ozturk Fincan GS, Vural IM, Ercan ZS, Sarioglu Y Tags: Eur J Pharmacol Source Type: journals
Effects of SCH23390 and spiperone administered into medial striatum and intermediate medial mesopallium on rewarding effects of morphine in day-old chicks.Email this article to a colleague.
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In this study, a 6-day conditioning schedule in day-old chicks with i.p. morphine (2mg/kg) was used to compare the effects of intracerebrally injected dopamine D1 receptor antagonist, SCH23390, and D(2) antagonist, spiperone. The antagonists were injected bilaterally (3ug/site) into either the medial striatum or the intermediate medial mesopallium, and tests were conducted on morphine-induced conditioned place preference or locomotor activity. The acquisition of place preference was significantly inhibited by SCH23390 in either the medial striatum or the intermediate medial mesopallium, but not by spiperone. However, in th...
Source: European Journal of Pharmacology - October 27, 2009 Category: Drugs & Pharmacology Authors: He X, Xiao L, Sui N Tags: Eur J Pharmacol Source Type: journals
Functional role of alpha(2)-adrenoceptor subtypes in the cooling-enhanced vasoconstriction of isolated cutaneous digital veins of the horse.Email this article to a colleague.
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Cooling-enhanced contractile responses in cutaneous arteries have been reported to involve the activation of alpha(2C)-adrenoceptors, but their role in cutaneous veins is not clearly understood. The aim was to pharmacologically characterize the subtype of postsynaptic alpha(2)-adrenoceptors in the equine digital vein mediating contraction at two temperatures. The increase in isometric tension of endothelium-denuded equine digital vein in response to UK-14304 was studied in the absence and presence of relatively selective alpha(2)-adrenoceptor antagonists at temperatures of either 30 degrees C (the peripheral digit temp...
Source: European Journal of Pharmacology - October 27, 2009 Category: Drugs & Pharmacology Authors: Zerpa H, Berhane Y, Elliott J, Bailey SR Tags: Eur J Pharmacol Source Type: journals
Effect of apocynin on NADPH oxidase-mediated oxidative stress-LOX-1-eNOS pathway in human endothelial cells exposed to high glucose.Email this article to a colleague.
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Hyperglycemia-induced generation of reactive oxygen species contributes to the development of proatherogenic changes and vasculopathy in diabetes. NADPH oxidase has been recognized as a major source of reactive oxygen species in the vasculature and the lectin-like oxLDL receptor-1 (LOX-1) appears to play a crucial role in the pathogenesis of diabetic endothelial dysfunction. The present study aimed to examine the relationships between the hyperglycemia-mediated NADPH oxidase-LOX-1 pathway activation and nitric oxide-mediated endothelial function. In addition, we investigated effect of the NADPH oxidase inhibitor, apocy...
Source: European Journal of Pharmacology - October 27, 2009 Category: Drugs & Pharmacology Authors: Taye A, Saad AH, Kumar AH, Morawietz H Tags: Eur J Pharmacol Source Type: journals
