Uptake of nicotine and extracellular space markers by isolated rat ganglia in relation to receptor activation.

1. Uptake of (3)H-nicotine by isolated rat superior cervical sympathetic (SCG) and nodose (NG) ganglia was measured in vitro. Depolarization of the ganglia by nicotine was measured electrically.2. Nicotine depolarized the SCG but not the NG. The mean ED50 for depolarization was 5.3 x 10(-6)M.3. Both ganglia accumulated nicotine when incubated in 3.1 x 10(-5)M(3)H-nicotine: after 30 min incubation the ratios of tissue to medium concentrations were (mean +/- S.E. of mean): SCG, 3.49 +/- 0.13; NG, 2.50 +/- 0.09.4. Total water contents, estimated by drying to constant weight, were: SCG, 83.8 +/- 0.12%; NG, 80.1 +/- 0.21%. Extracellular spaces, measured as (3)H-mannitol space, were: SCG, 38.8 +/- 1.3; NG, 40.3 +/- 0.8% wet weight. These values were not significantly altered by nicotine.5. Correction for tissue fluid spaces indicated that the ratio of the mean intracellular fluid concentration to the extracellular fluid concentration for (3)H-nicotine at 3.1 x 10(-5)M were: SCG, 7.4; NG, 5.6. The ratios were not altered in any consistent manner on varying the nicotine concentration between 3.1 x 10(-7) and 1.6 x 10(-4)M.6. When the nicotine concentration was sufficiently great (6.2 x 10(-6)M or more) to evoke large SCG depolarizations, hexamethonium (2.5 x 10(-3)M) reduced (3)H-nicotine uptake by the SCG by up to 19% without affecting uptake by the NG, and thereby reduced the uptake difference between the two ganglia. With nicotine concentrations <6.2 x 10(-6)M, hexamethonium did not modify uptake by either ganglion.7. It was concluded that nicotine may be concentrated within neurones, and that such intracellular accumulation may be augmented during depolarization induced by nicotine.