Evidence for carrier-mediated efflux of dopamine from corpus striatum

The results suggest that release of [3H]DA by sympathomimetic amines may be a carrier-mediated process, and the rate-limiting step in ouabain-induced release may involve inactivation of an enzyme such as Na+K+-ATPase which is coupled to the transport of sodium.

Abstract

This study was designed to further evaluate the hypothesis that the efflux of cytoplasmic dopamine from nerve endings of the corpus striatum can occur by carrier-mediated facilitated diffusion. Since dopamine (DA) and sodium ions are thought to be cotransported by the neuronal uptake carrier, the change in DA efflux upon alterations induced in the sodium gradient was observed. Ouabain was used to inhibit Na+K+-ATPase and thus increase intracellular sodium concentration, while metabolic inhibitors resulted in the same effect by reducing the amount of ATP available for Na+K+-ATPase. Rats were pretreated with reserpine and incubated with [3H]DA in the presence of pargyline so that the efflux of cytoplasmic [3H]DA could be assessed. Under these conditions, ouabain produced a concentration-related increase in the efflux of [3H]DA from nerve endings of the corpus striatum. The ouabain-induced release of [3H]DA was reduced by 10−M benztropine, a dopamine uptake inhibitor. Benztropine (10−5M) also reduced the increase in release of pHjDA when the same tissue preparation was incubated with the metabolic inhibitors sodium cyanide, iodoacetic acid and dinitrophenol. Ouabain at a concentration which caused slight release of [3H]DA potentiated the efflux produced by 3 × 10−6 M amphetamine, 3 × 10−6M unlabeled DA and 10−4M fenfluramine. These results suggest that release of [3H]DA by sympathomimetic amines may be a carrier-mediated process. The Q10 for 10−4 M ouabain-induced release of [3H]DA was much higher than the Q10 for the above processes and, therefore, the rate-limiting step in ouabain-induced release may involve inactivation of an enzyme such as Na+K+-ATPase which is coupled to the transport of sodium. Thus, by changing the availability of sodium with ouabain or metabolic inhibitors and by changing the cytoplasmic accessibility of the membrane carrier with benztropine or phenethylamines, the efflux of cytoplasmic [3H]da can be altered markedly.