The GR127935-sensitive 5-HT1 receptors mediating canine internal carotid vasoconstriction: resemblance to the 5-HT1B, but not to the 5-HT1D or 5-ht(1F), receptor subtype

1 This study has further investigated the pharmacological profile of the GR 127935-sensitive 5-HT1 receptors mediating vasoconstriction in the internal carotid bed of anaesthetized vagosympathectomized dogs. 2 One-minute intracarotid infusions of the agonists 5-hydroxytryptamine (5- HT; 0.1-10 mug min(-1); endogenous ligand) and sumatriptan (0.3-10 mug min( -1): 5-HT1B/1D), but not PNU-142633 (1-1000 mug min(-1); 5-HT1D) or LY34486 4 (1-1000 mug min(-1) 5-ht(1F)), produced dose-dependent decreases in inter nal carotid blood flow without changing blood pressure or heart rate. 3 The responses to 5-HT were apparently resistant to blockade by i.v. admin istration of the antagonists SB224289 (300 mug kg(-1) 5-HT1B), BRL15572 (30 0 mug kg(-1); 5-HT1D) or ritanserin (100 mug kg(-1); 5-HT2). In contrast, t he responses to sumatriptan were antagonized by SB224289, but not by BRL155 72. 4 In the animals receiving SB224289, but not those receiving BRL15572, the subsequent administration of ritanserin abolished the 5-HT-induced vasocons triction and unmasked vasodilator component. Similarly, in ritanserin-treat ed animals, the subsequent administration of SB224289, but not BRL15572, co mpletely blocked the 5-HT-induced vasoconstriction, revealing vasodilatatio n. In animals receiving initially BRL15572, the subsequent administration o f SB224289 did not affect (except at 10 mug min(-1)) the vasoconstrictor re sponses to 5-HT. 5 Notably, in animals pretreated with 1000 mug kg(-1) of mesulergine, a 5-H T2/7 receptor antagonist, 5-HT produced a dose-dependent vasoconstriction, which was practically abolished by SB224289. After BRL15572, no further blo ckade was produced and the subsequent administration of ritanserin was simi larly inactive. 6 These results suggest that the GR127935-sensitive 5-HT1 receptors mediati ng canine internal carotid vasoconstriction resemble the 5-HT1B but not the 5-HT1D or 5-ht(1F), receptor subtype.