title: Characterization of (+/-)(-)[3H]epibatidine binding to nicotinic cholinergic receptors in rat and human brain.
abstract: Epibatidine is an alkaloid that was first isolated from the skin of the Ecuadoran frog Epipedobates tricolor by Daly et al. [J. Am. Chem. Soc. 102:803-836 (1980)] and was found to have very high affinity for neuronal nicotinic receptors, where it acts as a potent agonist. Here we have measured and characterized the binding of (+/-)(-)[3H]epibatidine to nicotinic receptors in rat brain. In rat forebrain homogenates, (+/-)(-)[3H]epibatidine binds to two sites, with apparent affinities of 15 pM and 360 pM. Both of these binding sites have pharmacological profiles consistent with neuronal nicotinic receptors and a similar brain regional distribution. (+/-)(-)[3H]Epibatidine also binds to sites in rat adrenal gland, suggesting that it can label a subtype of nicotinic receptor found in peripheral ganglia as well as the subtype that predominates in brain. In human cerebral cortex as well, (+/-)(-)[3H]epibatidine binds two sites, one of which appears to have an affinity of < 1 pM. We conclude that (+/-)(-)[3H]epibatidine should be a very useful new tool for characterizing the properties and regulation of neuronal nicotinic receptors, including those not easily measurable with other radioligands.
authors.affiliation: Department of Pharmacology, Georgetown University School of Medicine, Washington, D. C. 20007, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Houghtling
authors.forename: M I
authors.initials: MI
authors.lastname: Dávila-García
authors.forename: K J
authors.initials: KJ
authors.lastname: Kellar
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism* / Q000493:pharmacokinetics; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006801:Humans; D008297:Male; D018722:Nicotinic Agonists / Q000378:metabolism* / Q000493:pharmacokinetics; D011725:Pyridines / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014018:Tissue Distribution; D014316:Tritium
chemical_list: D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D014316:Tritium; C082748:epibatidine