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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wilson, Richard J. Giles, Heather |
| Description | Author Affiliation: Wilson RJ ( Receptor Pharmacology Unit, Department of In-vitro Pharmacology, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK. rjw40122@gsk.com) |
| Abstract | Prostaglandin E(2) produced endothelium-independent relaxation of phenylephrine- and 5-HT-contracted piglet saphenous vein (PSV; pEC(50)=8.6+/-0.2; n=6). The prostanoid EP(4) receptor antagonist GW627368X (30-300 nM) produced parallel rightward displacement of PGE(2) concentration-effect (E/[A]) curves (pK(b)=9.2+/-0.2; slope=1). Higher concentrations of GW627368X did not produce further rightward shifts, revealing the presence of non-EP(4) prostanoid receptors. In all, 18 other prostanoid receptor agonists relaxed PSV in a concentration-related manner. Relative potencies of agonists most sensitive to 10 muM GW627368X (and therefore predominantly activating EP(4) receptors) correlated well with those at human recombinant EP(4) receptors in human embryonic kidney (HEK-293) cells (r(2)=0.74). In the presence of 10 microM GW627368X, the rank order of agonist relative potency matched that of the human recombinant EP(2) receptor in Chinese hamster ovary cells (r(2)=0.72). Iloprost, cicaprost and PGI(2) relaxed PSV maximally and were antagonised by 10 microM GW627368X, demonstrating that they were full EP(4) receptor agonists. Residual responses to these compounds in the presence of GW627368X suggested the presence of IP receptors.BW245C relaxed PSV maximally (pEC(50)=6.8+/-0.1). In the presence of 10 microM GW627368X, BW245C produced biphasic E/[A] curves (phase one pEC(50)=6.6; alpha=24%; phase two pEC(50)=5.1; alpha=112%). Phase two was antagonised by the DP receptor antagonist BW A868C (1 microM), demonstrating that BW245C is an agonist at DP and EP4 receptors. We conclude that PSV contains EP(4), EP(2), DP and IP receptors; IP receptor agonists are also porcine EP(4) receptor agonists. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 3 |
| Volume Number | 144 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2005-02-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Muscle, Smooth, Vascular Drug Effects Receptors, Prostaglandin Saphenous Vein Metabolism Acetylcholine Pharmacology Algorithms Animals Dinoprostone Iloprost In Vitro Techniques Isometric Contraction Muscle Relaxation Receptors, Immunologic Agonists Antagonists & Inhibitors Receptors, Prostaglandin E Receptors, Prostaglandin E, EP2 Subtype Receptors, Prostaglandin E, EP4 Subtype Swine Vasodilator Agents |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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