title: Selective 5-HT1B agonists identify the 5-HT autoreceptor in lumbar spinal cord of rat.
abstract: The purpose of the present study was to characterize the 5-HT autoreceptor in the lumbar spinal cord of the rat. The effect of selective 5-HT1A and 5-HT1B agonists on K+-evoked release of [3H]5-HT and the binding of [3H]5-HT were examined. The 5-HT1B compounds, mCPP and quipazine were more potent than exogenous 5-HT at decreasing K+-evoked release of [3H]5-HT in slices of spinal cord. The pEC40 values of 5-HT agonists tested, determined from release assays, significantly correlated with the relative affinities (pKD's) of these compounds for the binding of [3H]5-HT to the 5-HT1B receptor subtype in the presence of 2 microM 8-OHDPAT, as determined from radioligand binding studies (r = 0.98, P = 0.003). Conversely, the potencies of the 5-HT1A agonists 5-MeODMT and 8-OHDPAT, at the 5-HT autoreceptor, were negatively correlated (r = -0.77, P less than 0.10) with their potencies at displacing [3H]5-HT from the 5-HT1A subsite (binding of [3H]5-HT in the presence of 1 microM mCPP). Thus, the 5-HT autoreceptor in spinal cord appears to bear a significant pharmacological similarity to the 5-HT1B binding site. Further testing of the present results requires the development of new 5-HT1 agonists which are selective (1000-fold difference) for the 5-HT1A and 5-HT1B subsites.
authors.affiliation: University of Cincinnati College of Medicine, Division of Geriatrics, Cincinnati, OH 45267-0555.
authors.forename: R M
authors.initials: RM
authors.lastname: Murphy
authors.forename: F P
authors.initials: FP
authors.lastname: Zemlan
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000032:analysis* / Q000145:classification / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
chemical_list: D011985:Receptors, Serotonin; D012701:Serotonin; D011188:Potassium