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 const ricts porcine carotid arteriovenous anastomoses via 5-HT1-like receptors, i dentical to 5-HT1B/1D receptors. The recent availability of silent antagoni sts selective for the 5-HT1B (8B224289) and 5-HT1D (BRL15572) receptor led us to further analyse the nature of receptors involved. 2 In pentobarbitone-anaesthetized, bilaterally vagosympathectomized pigs, s umatriptan (30, 100 and 300 pg kg(-1), i.v.) dose-dependently decreased car otid arteriovenous anastomotic conductance by up to 70+/-5%. 3 The dose-related decreases in carotid arteriovenous anastomotic conductan ce 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 SB2242 89. The highest dose of SB224289 did not attenuate the hypertension, tachyc ardia or increases in carotid blood flow induced by bolus injections of nor adrenaline (0.1-3 mu g kg(-1), i.v.). 4 The results indicate that sumatriptan constricts porcine carotid arteriov enous anastomoses primarily via 5-HT1B, but not via 5-HT1D receptors.