Abstract

The effects of various pharmacological agents on [ 14C]-nicotine accumulation, distribution and movements in rat brain cortex, striatum, hypothalamus and cerebellum slices were studied. When present during incubation, mecamylamine (2.0 m m) decreased the [ 14-nicotine tissue space and both mecamylamine and nonradioactive nicotine (0.62 m m) acted primarily to decrease the amount of [ 14C]-nicotine present in the slower component of a two-component washout of [ 14C]-nicotine. Procaine (3.67 m m) also decreased [ 14C]-nicotine uptake; this decrease occurred almost exclusively within the slower component. Lobeline (0.62 m m), physostigmine (1.0 m m) and, to a lesser extent, metanephrine (1.0 mm) also decreased the [ 14C]-nicotine tissue space in a competitive manner. No direct interaction with various cholinergic agents was demonstrated. When added during washout of [ 14C]-nicotine, both mecamylamine and procaine increased [ 14C]-nicotine efflux. It appears that the agents employed compete with [ 14C]-nicotine for cellular binding sites or, in the case of procaine, might possibly also inhibit access of [ 14C-nicotine to the intracellular sites.

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