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Multiple 5‐HT receptors in the guinea‐pig superior cervical ganglion
Author(s) -
Watkins Clare J.,
Newberry Nigel R.
Publication year - 1996
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.1476-5381.1996.tb15149.x
Subject(s) - ketanserin , receptor , 5 ht receptor , mianserin , spiperone , pharmacology , chemistry , serotonin , superior cervical ganglion , serotonin antagonists , endocrinology , medicine , biology , biochemistry
1 We have studied the pharmacology of the depolarization by 5‐hydroxytryptamine (5‐HT) of the guinea‐pig isolated superior cervical ganglion (SCG) using the grease‐gap technique. We studied the effects of selective and non‐selective antagonists on the responses to 5‐HT and other 5‐HT receptor agonists. 2 We have extended the pharmacology of the 5‐HT 3 receptor in this preparation by studying the effects of granisetron, BRL 46470 and mianserin on the concentration‐response curve (CRC) to 2‐methyl‐5‐HT. As with other 5‐HT 3 receptor antagonists, these compounds exhibited a lower affinity for guinea‐pig 5‐HT 3 receptors than for rat 5‐HT 3 receptors. 3 We have confirmed that low concentrations of 5‐HT (≤ 1 μ m ) mediate ketanserin‐sensitive responses and higher concentrations of 5‐HT also recruit 5‐HT 3 receptors. The responses to low concentrations of 5‐HT were antagonized by low concentrations of ketanserin, spiperone, mianserin, DOI and LSD indicating probably mediation by 5‐HT 2A receptors. At high concentrations, the hallucinogen, DOI, but not LSD, evoked a ketanserin‐sensitive depolarization. 4 Although mianserin could bind to the 5‐HT 2A receptors in this preparation, we could not demonstrate a down‐regulation of depolarizations evoked by these receptors after a 10 day oral treatment with mianserin (10 mg kg −1 , daily). 5 5‐Carboxamidotryptamine (5‐CT) evoked a prolonged depolarization. Although high concentrations of 5‐CT (≥1 μ m ) appeared to activate 5‐HT 2A receptors, lower concentrations of 5‐CT evoked a response with a distinct pharmacology. After studying the action of 20 selective and non‐selective 5‐HT receptor ligands we believe that this response may be mediated by a novel receptor; but its pharmacology is closest to that of receptors in the 5‐HT 2 receptor family. Like 5‐CT, 5‐HT (3–300 μ m ) could evoke an LSD‐sensitive response in the presence of the 5‐HT 2 receptor antagonist, ketanserin and the 5‐HT 3 receptor antagonist, tropisetron (all 1 μ m ). 6 We conclude that 5‐HT activates three pharmacologically distinct receptors to depolarize the guinea‐pig SCG. Low concentrations of 5‐HT appear to activate 5‐HT 2A receptors. Higher concentrations of 5‐HT also activate 5‐HT 3 receptors and a possible novel 5‐HT receptor. The novel receptor could be a species homologue of a 5‐HT 2 receptor or an, as yet, unclassified 5‐HT receptor.