Active Transport of3H-Bretylium in the Rat Vas Deferens in vitro

Abstract

The uptake and efflux of ³H-bretylium in slices of the rat vas deferens were examined. The uptake of bretylium was temperature, Na⁺and Cl^-dependent, sensitive to 6-hydroxydopamine but insensitive to reserpine. The uptake was inhibited by desipramine, (+)-amphetamine, imipramine methiodide and cocaine, whereas the local anaesthetics millicaine and lidocaine were poor inhibitors. The spontaneous efflux was very slow at 0°C and slow at 37°. Desipramine accelerated the efflux probably by inhibiting the re-uptake of bretylium. (+)-Amphetamine, low external Na⁺, high external K⁺and ouabain caused a pronounced increase in the efflux at 37°C but was almost without effect at 0°C. The efflux evoked by (+)-amphetamine, low Na⁺and ouabain was inhibited by desipramine, imipramine methiodide and cocaine, whereas millicaine and lidocaine had very poor effects. The increase of bretylium efflux by hypertonic K⁺was only slightly inhibited by desipramine and partially antagonized by omission of Ca²⁺in the medium. The results obtained indicate that bretylium was taken up in noradrenergic neurones by the noradrenaline transport mechanism and that the efflux of bretylium produced by (+)-amphetamine, low external Na⁺, low external Cl^-and by ouabain occurred by the same transport mechanism as the uptake but now working in the outward direction whereas the efflux induced by high K⁺seemed to occur mainly with another mechanism.