title: Activity of alpha7-selective agonists at nicotinic and serotonin 5HT3 receptors expressed in Xenopus oocytes.
abstract: Nicotinic receptors containing alpha7 subunits are widely distributed in the central nervous system and are thought to be involved in a number of functions. However, it has been difficult to study alpha7-containing receptors in vivo because of a paucity of selective agonists. A new spirooxazolidinone compound, AR-R17779, was recently described as potent agonist at alpha7 receptors, but electrophysiological studies at other types of nicotinic receptors have not been carried out. We characterized the activity of AR-R17779 at alpha7, alpha4beta2, alpha3beta4, alpha3beta2, alpha3beta2alpha5 receptors expressed in Xenopus oocytes. In addition, since there is significant homology between nicotinic alpha7 and serotonin 5HT(3) receptors, the activity of AR-R17779 at expressed 5HT(3a) receptors was also examined. Finally, actions of tropisetron and ondansetron, two 5HT(3) antagonists, were explored. AR-R17779 was found to activate alpha7 receptors, but had no activity at other types of nicotinic receptors, and also had no activity at 5HT(3a) receptors. Tropisetron activated, while ondansetron acted as an antagonist, at alpha7 nicotinic receptors. The two 5HT(3) antagonists also acted as antagonists at alpha4beta2 and alpha3beta4 nicotinic receptors. Thus, AR-R17779 was confirmed to be a selective nicotinic alpha7 receptor agonist and to be without activity at 5HT(3) receptors. In contrast, the actions of tropisetron and ondansetron on nicotinic receptors were complex.
authors.affiliation: Department of Pharmacology, University of Florida, PO Box 100267, 1600 SW Archer Rd, Gainesville, FL 32610, USA. rpapke@college.med.ufl.edu
authors.forename: R L
authors.initials: RL
authors.lastname: Papke
authors.forename: Julia K
authors.initials: JK
authors.lastname: Porter Papke
authors.forename: G M
authors.initials: GM
authors.lastname: Rose
mesh_terms: D000818:Animals; D001952:Bridged-Ring Compounds / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000378:metabolism / Q000494:pharmacology*; D017294:Ondansetron / Q000378:metabolism / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology*; D013141:Spiro Compounds / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000077526:Tropisetron; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C408128:AR-R 17779; D001952:Bridged-Ring Compounds; D007211:Indoles; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D013141:Spiro Compounds; D064569:alpha7 Nicotinic Acetylcholine Receptor; D017294:Ondansetron; D000077526:Tropisetron