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.
D062365:Aminobenzoates / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001949:Bretylium Compounds / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D062425:Hydroxybenzoate Ethers; D006892:Hydroxydopamines / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000378:metabolism*; D013696:Temperature; D014649:Vas Deferens / Q000378:metabolism*; D062368:meta-Aminobenzoates
D062365:Aminobenzoates; D000779:Anesthetics, Local; D001949:Bretylium Compounds; D002712:Chlorides; D062425:Hydroxybenzoate Ethers; D006892:Hydroxydopamines; D062368:meta-Aminobenzoates; C012774:bethoxycaine; D010042:Ouabain; D012110:Reserpine; D008012:Lidocaine; D012964:Sodium; D000661:Amphetamine; D003042:Cocaine; D007099:Imipramine; D003891:Desipramine