Lack of stereoselectivity in ability of nicotine to release dopamine from rat synaptosomal preparations.
Both the naturally occurring (-)-isomer and the synthetic (+)-isomer of nicotine caused release of 3H from a crude synaptosomal fraction of rat brain preincubated with [3H]dopamine. The isomers were equipotent in producing this response, which was concentration-dependent, a significant effect on the fractional release of dopamine being observed at 10(-4) M nicotine. The effect did not appear to be the result of synaptosomal damage, as levels of the intrasynaptosomal marker lactate dehydrogenase did not increase in the supernatant. Nicotine-induced release was inhibited by removal of external Ca2+ and by the presence in vitro of pempidine (230 microM). Neither hexamethonium (500 microM) in vitro nor the chronic administration of (-)-nicotine in vivo had any effect on the nicotine-induced release of [3H]dopamine. It is concluded that nicotine exerts this effect via a presynaptic nicotinic receptor of the "ganglionic" type, but that this receptor differs from that in the periphery by showing a relative lack of stereospecificity. There is no evidence of a functional "down regulation" in this receptor on chronic exposure to nicotine in vivo.
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D010393:Pempidine / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D006584:Hexamethonium Compounds; D009538:Nicotine; D010393:Pempidine; D004298:Dopamine