Investigation of the role of 5-HT1B and 5-HT1D receptors in the sumatriptan-induced constriction of porcine carotid arteriovenous anastomoses

1 It has previously been shown that the antimigraine drug sumatriptan constricts porcine carotid arteriovenous anastomoses via 5-HT(1)-like receptors, identical to 5-HT(1B/1D) receptors. The recent availability of silent antagonists selective for the 5-HT(1B) (8B224289) and 5-HT(1D) (BRL15572) receptor led us to further analyse the nature of receptors involved. 2 In pentobarbitone-anaesthetized, bilaterally vagosympathectomized pigs, sumatriptan (30, 100 and 300 pg kg(-1), i.v.) dose-dependently decreased carotid arteriovenous anastomotic conductance by up to 70+/-5%. 3 The dose-related decreases in carotid arteriovenous anastomotic conductance by sumatriptan (30, 100 and 300 mu g kg(-1), i.v.) remained unchanged in animals treated (i.v.) with 1 mg kg(-1) of BRL15572 (maximum decrease: 72+/-3%), but were significantly attenuated by 1 mg kg(-1) (maximum decrease: 30+/-11%) and abolished by 3 mg kg(-1) (maximum decrease: 3+/-7%) of SB224289. The highest dose of SB224289 did not attenuate the hypertension, tachycardia or increases in carotid blood flow induced by bolus injections of noradrenaline (0.1-3 mu g kg(-1), i.v.). 4 The results indicate that sumatriptan constricts porcine carotid arteriovenous anastomoses primarily via 5-HT(1B), but not via 5-HT(1D) receptors.