Characterization of 5-HT receptors mediating contraction of canine and primate basilar artery by use of GR43175, a selective 5-HT1-like receptor agonist.
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, alpha-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 greater than or equal to 5-HT greater than GR43175 greater than alpha-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 alpha-methyl 5-HT. 3. In canine basilar artery, ketanserin (0.1-1 microM) 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 microM), MDL72222 (1 microM) or cyanopindolol (1 microM). However, the effects of 5-HT and GR43175 were specifically antagonized by methiothepin (0.1 microM); the mean agonist concentration-ratios were 33 and 48 respectively. 4. In primate basilar artery, ketanserin (1 microM) again caused a small depression of the 5-HT maximum response but had not effect against GR43175-induced contractions. In contrast, methiothepin (0.1 microM) 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 prepAarations which contribute to the contractile effects of 5-HT.
Connor
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HE
Department of Cardiovascular Pharmacology, Glaxo Group Research Ltd, Ware, Hertfordshire.
Feniuk
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Humphrey
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PP
D000818:Animals; D001488:Basilar Artery; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008252:Macaca fascicularis; D008297:Male; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D018170:Sumatriptan; D014661:Vasoconstriction / Q000187:drug effects*
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D012701:Serotonin; D018170:Sumatriptan; C047087:5-carboxamidotryptamine