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.