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

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) greater than 5-HT identical to methysergide greater than GR43175 much greater than 8-OHDPAT much greater than 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 F2 alpha, 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-HT1A and 5-HT1B 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.