Evidence for 5-HT1B/1D and 5-HT2A receptors mediating constriction of the canine internal carotid circulation

1 The present study has investigated the preliminary pharmacological profil e of the receptors mediating vasoconstriction to 5-hydroxytryptamine (5-HT) in the internal carotid bed of vagosympathectomised dogs. 2 One minute intracarotid infusions of the agonists 5-HT (0.1-10 mug min(-1 )), sumatriptan (0.3-10 mug min(-1); 5-HT1B/1D), 5-methoxytryptamine (1-100 mug min(-1) 5-HT1, 5-HT2, 5-HT4, 5-ht(6) and 5-HT7) or DOI (0.31-10 mug mi n(-1); 5-HT2), but not 5-carbaxamihotryptamine (0.01-0.3 mug min(-1); 5-HT1 , 5-ht(5A) and 5-HT7), 1-(m-chlorophenyl)-biguanide (mCPBG; 1-1000 mug min( -1); 5-HT3) or cisapride (1-1000 mug min(-1); 5-HT4), resulted in dose-depe ndent decreases in internal carotid blood flow, without changing blood pres sure or heart rate. 3 The vasoconstrictor responses to 5-MT, which remained unaffected after sa line, were resistant to blockade by i.v. administration of the antagonists ritanserin (100 mug kg(-1); 5-HT2A/2B/2C) in combination with tropisetron ( 3000 mug kg(-1); 5-HT3/4) Or the cyclo-oxygenase inhibitor, indomethacin (5 000 mug kg(-1)), but were abolished by the 5-HT1B/1D receptor antagonist, G R127935 (30 mug kg(-1)). Interestingly, after administration of GR127935, t he subsequent administration of ritanserin unmasked a dose-dependent vasodi lator component. GR127935 or saline did not practically modify the vasocons trictor effects of 5-MeO-T. In animals receiving GR127935, the subsequent a dministration of ritanserin abolished the vasoconstrictor responses to 5-Me O-T unmasking a dose-dependent vasodilator component. 4 The vasoconstriction induced by sumatriptan was antagonized by GR127935, but not by ritanserin. Furthermore, ritanserin (100 mug kg(-1)) or ketanser in (100 mug kg(-1); 5-HT2A), but not GR127935, abolished DOI-induced vasoco nstrictor responses. 5 The above results suggest that 5-HT-induced internal carotid vasoconstric tion is predominantly mediated by 5-HT1B/1D and 5-HT2A receptors.