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

Abstract

1 Uptake of ³H-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 × 10⁻⁶m. 3 Both ganglia accumulated nicotine when incubated in 3·1 × 10⁻⁵m ³H-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 ³H-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 ³H-nicotine at 3·1 × 10⁻⁵m were: SCG, 7·4; NG, 5·6. The ratios were not altered in any consistent manner on varying the nicotine concentration between 3·1 × 10⁻⁷ and 1·6 × 10⁻⁴m. 6 When the nicotine concentration was sufficiently great (6·2 × 10⁻⁶m or more) to evoke large SCG depolarizations, hexamethonium (2·5 × 10⁻³m) reduced ³H-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 −6m, 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.