5‐HT1‐like receptors mediate 5‐hydroxytryptamine‐induced contraction of human isolated basilar artery

Abstract

1 The 5-hydroxytryptamine (5-HT) receptor mediating contraction of endothelium denuded human basilar artery has been characterized in vitro. 2 5-HT and a variety of 5-HT agonists contracted human isolated basilar artery with a rank order of agonist potency, 5-carboxamidotryptamine (5-CT) > 5-HT = methysergide > GR43175 > 8-OHDPAT > 2-methyl-5-HT. The maximum response produced by these agonists differed. 3 None of the agonists relaxed human basilar artery when tone was elevated with prostaglandin F_2α, indeed further contraction was seen. 4 The contractile responses of human basilar artery to 5-HT and the selective 5-HT₁-like agonist GR43175 were highly reproducible whilst those to 5-CT were not. 5 The contractile response to both 5-HT and GR43175 was resistant to antagonism by ketanserin and GR38032, thus excluding activation of 5-HT₂ and 5-HT₃ receptors. The contractile action of 5-HT and GR43175 was also not antagonized by (±)-cyanopindolol, excluding the activation of receptors similar to 5-HT_1A and 5-HT_1B recognition sites identified in ligand binding studies. 6 In marked contrast, methiothepin was a potent antagonist of the contractile actions of both 5-HT and GR43175, with a pA₂ value of 8.8 against both agonists. Methiothepin (100 nm) had no effect on the contractile response to the thromboxane A₂-mimetic U46619. 7 We conclude that 5-HT and GR43175 contract the human isolated basilar artery by activating the same receptor type. This receptor appears identical to the 5-HT₁-like receptor causing contraction of the dog isolated saphenous vein and cerebral blood vessels from the dog and primate.