Nicotine washout rates from isolated rat ganglia in relation to recovery from nicotine depolarization.

1. Isolated rat superior cervical ganglia recovered more slowly from the depolarizing action of nicotine than from that of carbachol or acetylcholine. This was due to sustained high nicotine concentrations in the vicinity of the receptors, since recovery was hastened by adding hexamethonium to the washout fluid.2. Ganglia incubated for 4 min in 80 muM (3)H-nicotine accumulated nicotine to a level exceeding the extracellular space, as judged from the uptake of (3)H-mannitol.3. The subsequent efflux of (3)H-nicotine into non-radioactive solution could be largely resolved into two exponential components, with rate constants of 0.55+/-0.04 and 0.094+/-0.007 min(-1). The former was similar to that for total mannitol efflux, and so might be largely ascribed to clearance of extracellular nicotine. The slower efflux might be due to clearance from intracellular compartments. Nicotine efflux rates were not affected by hexamethonium indicating that receptor-activation did not modify the slow efflux.4. Efflux of choline compounds ((3)H-acetylcholine, (3)H-choline and (3)H-carbachol) showed an additional, very slow component (rate constant 0.001 to 0.002 min(-1)).5. It was suggested that slow efflux of intracellular nicotine might sustain depolarization on washing by maintaining high perineuronal concentrations of nicotine. With choline compounds the efflux rate from such sources may be too slow to affect perineuronal concentrations.