Interaction between dopamine influx and efflux in rat striatal synaptosomes |
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Authors: | Hans Schoemaker Victor J Nickolson |
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Institution: | Department CNS Pharmacology, Scientific Development Group Organon, Oss, The Netherlands |
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Abstract: | Exchange release has previously been proposed as the mechanism by which dopamine is transported over the synaptosomal membrane. An increase in carrier-mediated dopamine release should therefore result in an enhanced rate of synaptosomal dopamine uptake. In order to test this hypothesis, rat striatal synaptosomes were incubated with 14C-dopamine until equilibrium. Then, the 14C-dopamine concentration in the medium was reduced in order to elicit various rates of net dopamine efflux, while influx was monitored using tracer amounts of 3H-dopamine. Dopamine release was concentration dependent and saturable and thus may be carrier-mediated. In contrast to that expected for a mechanism of exchange release, dopamine influx was depressed as compared to equilibrium conditions. Furthermore, nomifensine, a specific inhibitor of dopamine influx, did not attenuate dopamine efflux. It is concluded that dopamine transport over the synaptosomal membrane may not be via a mechanism of strict exchange release. |
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