Enhanced prostaglandin synthesis contributes to the venoconstrictor activity of ergotamine.
Spiral strips from dog saphenous veins were contracted by 2.5 X 10(-9) M ergotamine, a concentration giving about 50% of maximal response. Phentolamine (3.6 X 10(-6) M) reduced these effects by 60% and indomethacin (2.8 X 10(-7) M) by 30%. Indomethacin was more effective in reducing ergotamine-induced increase of prostaglandin E-like activity in the bathing fluid than those induced by noradrenaline or potassium chloride. Arachidonic acid was more effective in increasing tension in ergotamine-stimulated than in noradrenaline- or potassium-stimulated veins. These findings suggest that the long-lasting venoconstrictor activity of ergotamine is mediated mainly by alpha-adrenoceptors but that enhanced formation of prostaglandin E-like substance(s) may also contribute.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001681:Biological Assay; D002845:Chromatography; D003864:Depression, Chemical; D004285:Dogs; D004347:Drug Interactions; D004878:Ergotamine / Q000037:antagonists & inhibitors*; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011453:Prostaglandins / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D011941:Receptors, Adrenergic; D012501:Saphenous Vein / Q000187:drug effects; D013268:Stimulation, Chemical; D014680:Veins / Q000187:drug effects*
D001095:Arachidonic Acids; D011453:Prostaglandins; D011941:Receptors, Adrenergic; D011189:Potassium Chloride; D004878:Ergotamine; D009638:Norepinephrine; D007213:Indomethacin; D010646:Phentolamine