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Activation of the 5‐HT 1c receptor expressed in Xenopus oocytes by the benzazepines SCH 23390 and SKF 38393
Author(s) -
Briggs Clark A.,
Pollock Nancy J.,
Frail Donald E.,
Paxson Cheryl L.,
Rakowski Robert F.,
Kang Chae Hee,
Kebabian John W.
Publication year - 1991
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.1476-5381.1991.tb12546.x
Subject(s) - agonist , sch 23390 , partial agonist , xenopus , receptor , 5 ht receptor , chemistry , medicine , endocrinology , biology , pharmacology , serotonin , biochemistry , gene
1 A cloned 5‐HT 1C receptor expressed in Xenopus laevis oocytes was used to characterize the action of four dopamine D 1 ‐selective benzazepines at the 5‐HT 1C receptor. Additionally, the apparent binding of the D 1 ‐selective benzazepines to 5‐HT 1C receptors was measured in the choroid plexus of the pig. 2 In voltage‐clamped oocytes expressing the cloned 5‐HT 1C receptor, 5‐hydroxytryptamine (5‐HT) elicited a characteristic inward current response with an EC 50 of 13 n m . SCH 23390 acted as a stereoselective agonist (or partial agonist) with an EC 50 of about 550 n m . SKF 38393 (1 μ m –1 m m ), SKF 77434 (100 μ m ), and SKF 82958 (100 μ m ) also acted as agonists (or partial agonists) at the cloned 5‐HT 1C receptor. SKF 38393 was not stereoselective at the 5‐HT 1C receptor. 3 The response to SCH 23390 activated slowly and, although the response contained many oscillations characteristic of the activation of the phosphatidylinositol signal transduction system, SCH 23390 rarely elicited the rapid spike‐like response seen routinely in response to 5‐HT. However, the responses to SKF 38393, SKF 77434, and SKF 82958 were identical in appearance to the response to 5‐HT, except that the responses to the benzazepines were smaller. These comparisons were made by applying both a benzazepine and 5‐HT to each individual oocyte expressing the cloned 5‐HT 1C receptor. 4 Consistent with the responses measured in oocytes, SCH 23390 bound stereoselectively to 5‐HT 1C receptors in the choroid plexus of the pig ( K i = 6.3 n m ), and SKF 38393 bound non‐stereoselectively with lower affinity ( K i = 2.0–2.2 μ m ). 5 It is concluded that while these benzazepines demonstrate selectivity for the dopamine D 1 receptor, they also can act as agonists or partial agonists at the 5‐HT 1C receptor in situ and as expressed in Xenopus oocytes. The oocyte expression system is useful for studies of the functional pharmacology of these 5‐HT 1C receptors. Information about the pharmacological actions and variations in stereoselectivity among dopamine and 5‐HT receptors should be of interest in modelling the interactions of ligands with these G‐protein coupled receptors, and in the testing of such models through receptor mutagenesis.;