Active transport of 3H-bretylium in the rat vas deferens in vitro.

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 degrees C and slow at 37 degrees. 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 degrees C but was almost without effect at 0 degrees 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.