Sumatriptan (GR43175) inhibits cyclic-AMP accumulation in dog isolated saphenous vein.
Sumatriptan (GR43175) contracts rings of dog isolated saphenous vein by an action at 5-HT1-like receptors. We have now examined the effects of sumatriptan on prostaglandin E2(PGE2)-stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in this tissue. Sumatriptan and 5-hydroxytryptamine (5-HT) produced a concentration-dependent inhibition of PGE2-stimulated cyclic AMP accumulation (EC50 values of 250 nM and 80 nM respectively), responses that were mimicked by 5-carboxamidotryptamine but not by U-46619 or methoxamine. The response to sumatriptan (1 microM) was antagonised by methiothepin (1 microM), but not by metergoline (0.1 microM), spiperone (1 microM) or ondansetron (GR38032, 1 microM). These results suggest that 5-HT1-like receptors which mediate contraction of the dog isolated saphenous vein are negatively coupled to adenylate cyclase in this preparation.
Sumner
M J
MJ
Pharmacology Division, Glaxo Group Research Ltd., Ware, Hertfordshire.
Humphrey
P P
PP
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D018170:Sumatriptan
D007211:Indoles; D011450:Prostaglandin Endoperoxides, Synthetic; D013449:Sulfonamides; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D018170:Sumatriptan; D000242:Cyclic AMP; D008729:Methoxamine; D015232:Dinoprostone