Characterization of 5-HT receptors mediating constriction of porcine carotid arteriovenous anastomoses;: Involvement of 5HT1B/1D and novel receptors

1 It was previously shown that porcine cranial arteriovenous anastomoses (AVAs) constrict to 5-hydroxytryptamine (5-HT), ergotamine, dihydroergotamine, as well as sumatriptan and that sumatriptan acts exclusively via 5-HT(1B/1D) receptors. The present study was devoted to establish the contribution of 5-HT(1B/1D) receptors in the constriction of AVAs elicited by 5-HT (in presence of 0.5 mg kg(-1) ketanserin), ergotamine and dihydroergotamine in anaesthetized pigs. 2 Intracarotid infusion of 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 AVA and increased nutrient blood flows and vascular conductances. The vasodilator response to 5-HT, observed mainly in the skin and ear, was much more prominent than that of the ergot alkaloids. 3 Treatment with the 5-HT(1B/1D) receptor antagonist GR127935 (0.5 mg kg(-1), i.v.) significantly attenuated both ergot-induced AVA constriction and arteriolar dilatation, whereas GR127935 only slightly affected the carotid vascular effects of 5-HT. 4 The results suggest that 5-HT constricts carotid AVAs primarily via receptors, which seem to differ from those (5-HT(1B/1D)) stimulated by sumatriptan. The ergot alkaloids produce AVA constriction for a substantial part via 5-HT(1B/1D) receptors, but also stimulate unidentified receptors. Both these non-5-HT(1B/1D) receptors may be targets for the development of novel antimigraine drugs. 5 The moderate vasodilator response to the ergot derivatives seems to be mediated, at least in part, by 5-HT(1B/1D) receptors, whereas the arteriolar dilatation caused by 5-HT maybe mediated by other, possibly 5-HT(7) receptors.