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5‐HT 1 ‐like receptors mediate 5‐hydroxytryptamine‐induced contraction of human isolated basilar artery
Author(s) -
Parsons Andrew A.,
Whalley Eric T.,
Feniuk Wasyl,
Connor Helen E.,
Humphrey Patrick P.A.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb11835.x
Subject(s) - methysergide , ketanserin , basilar artery , medicine , endocrinology , agonist , receptor , contraction (grammar) , 5 ht receptor , biology , serotonin , chemistry
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‐HT 1 ‐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‐HT 2 and 5‐HT 3 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 pA 2 value of 8.8 against both agonists. Methiothepin (100 n m ) had no effect on the contractile response to the thromboxane A 2 ‐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‐HT 1 ‐like receptor causing contraction of the dog isolated saphenous vein and cerebral blood vessels from the dog and primate.