Characterization of 5‐HT receptors mediating contraction of canine and primate basilar artery by use of GR43175, a selective 5‐HT1‐like receptor agonist

Abstract

1 The aim of this study was to characterize the 5-hydroxytryptamine (5-HT) receptor which mediates contraction of canine and primate isolated basilar artery by use of a variety of selective 5-HT agonists and antagonists. 2 5-HT, α-methyl 5-HT and the selective 5-HT₁-like receptor agonists, GR43175 and 5-carboxamidotryptamine (5-CT), each caused contraction of canine and primate basilar artery with a rank order of agonist potency of 5-CT ≥ 5-HT > GR43175 > α-methyl 5-HT. The 5-HT₁-like receptor agonists, GR43175 and 5-CT, produced maximum effects which were less than that produced by 5-HT or α-methyl 5-HT. 3 In canine basilar artery, ketanserin (0.1–1 μm) caused some depression of the maximum effect of 5-HT but produced little or no shift of the concentration-effect curve. The contractile effects of GR43175 were not modified by ketanserin (1 μm), MDL72222 (1 μm) or cyanopindolol (1 μm). However, the effects of 5-HT and GR43175 were specifically antagonized by methiothepin (0.1 μm); the mean agonist concentration-ratios were 33 and 48 respectively. 4 In primate basilar artery, ketanserin (1 μm) again caused a small depression of the 5-HT maximum response but had no effect against GR43175-induced contractions. In contrast, methiothepin (0.1 μm) antagonized both 5-HT- and GR43175-induced contractions; the mean agonist concentration-ratios were 35 for both. 5 These results demonstrate that a large component of the effects of 5-HT in canine and primate basilar artery is produced by stimulation of a 5-HT₁-like receptor. This receptor can be characterized by the high potency of the novel, selective agonist, GR43175, and susceptibility to blockade by methiothepin. However, there also appears to be a population of 5-HT₂ receptors in these pre-pAarations which contribute to the contractile effects of 5-HT.