CHARACTERIZATION OF (+ -)-[H-3]EPIBATIDINE BINDING TO NICOTINIC CHOLINERGIC RECEPTORS IN RAT AND HUMAN BRAIN/

Epibatidine is an alkaloid that was first isolated from the skin of th e Ecuadoran frog Epipedobates tricolor by Daly el al. [J. Am. Chem. Se c. 102:803-836 (1980)] and was found to have very high affinity for ne uronal nicotinic receptors, where it acts as a potent agonist. Here we have measured and characterized the binding of (+/-)-[H-3]epibatidine to nicotinic receptors in rat brain. In rat forebrain homogenates, (/-)-[H-3]epibatidine binds to two sites, with apparent affinities of 1 5 pM and 360 pM. Both of these binding sites have pharmacological prof iles consistent with neuronal nicotinic receptors and a similar brain regional distribution. (+/-)-[H-3]Epibatidine also binds to sites in r at adrenal gland, suggesting that it can label a subtype of nicotinic receptor found in peripheral ganglia as well as the subtype that predo minates in brain. In human cerebral cortex as well, (+/-)-[H-3]epibati dine binds two sites, one of which appears to have an affinity of < 1 pM. We conclude that (+/-)-[H-3]epibatidine should be a very useful ne w tool for characterizing the properties and regulation of neuronal ni cotinic receptors, including those not easily measurable with other ra dioligands.