CHARACTERIZATION OF 5-HT RECEPTORS MEDIATING CONSTRICTION OF PORCINE CAROTID ARTERIOVENOUS ANASTOMOSES - INVOLVEMENT OF 5HT(1B 1D) AND NOVEL RECEPTORS/

1 It was previously shown that porcine cranial arteriovenous anastomos es (AVAs) constrict to 5-hydroxytryptamine (5-HT), ergotamine, dihydro ergotamine, as well as sumatriptan and that sumatriptan acts exclusive ly via 5-HT1B/1D receptors. The present study was devoted to establish the contribution of 5-HT1B/1D receptors in the constriction of AVAs e licited by 5-HT (in presence of 0.5 mg kg(-1) ketanserin), ergotamine and dihydroergotamine in anaesthetized pigs. 2 Intracarotid infusion o f 5-HT (2 mu g kg(-1) min(-1)) and intravenous doses of ergotamine (2. 5-20 mu g kg(-1)) and dihydroergotamine (3-100 mu g kg(-1)) reduced AV A and increased nutrient blood flows and vascular conductances. The va sodilator response to 5-HT, observed mainly in the skin and ear, was m uch more prominent than that of the ergot alkaloids. 3 Treatment with the 5-HT1B/1D receptor antagonist GR127935 (0.5 mg kg(-1), i.v.) signi ficantly attenuated both ergot-induced AVA constriction and arteriolar dilatation, whereas GR127935 only slightly affected the carotid vascu lar effects of 5-HT. 4 The results suggest that 5-HT constricts caroti d AVAs primarily via receptors, which seem to differ from those (5-HT1 B/1D) stimulated by sumatriptan. The ergot alkaloids produce AVA const riction for a substantial part via 5-HT1B/1D receptors, but also stimu late unidentified receptors. Both these non-5-HT1B/1D receptors may be targets for the development of novel antimigraine drugs. 5 The modera te vasodilator response to the ergot derivatives seems to be mediated, at least in part, by 5-HT1B/1D receptors, whereas the arteriolar dila tation caused by 5-HT maybe mediated by other, possibly 5-HT7 receptor s.