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Dopamine transporter mediated release of dopamine: Role of chloride
Author(s) -
Sitges M.,
Reyes A.,
Chiu L. M.
Publication year - 1994
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490390103
Subject(s) - nomifensine , depolarization , dopamine , bupropion , chemistry , pharmacology , dopamine uptake inhibitors , dopamine transporter , reuptake , biophysics , synaptosome , endocrinology , in vitro , dopaminergic , biochemistry , receptor , biology , medicine , serotonin , pathology , smoking cessation
Using a rapid (0.5 ml/min) flow rate superfusion system, the dopamine (DA) transporter mediated release of DA is further explored, and compared to the depolarization evoked release of DA in rat striatal synaptosomes preloaded with radioactive DA ( 3 H‐DA). In this system external DA in the low μM range efficaciously releases the preloaded transmitter, the maximal response being reached at 3 μM DA. The external DA stimulated release is Ca 2+ ‐independent, Cl − ‐dependent, and blocked by both bupropion and nomifensine. The atypical antidepressant bupropion inhibits 3 H‐DA accumulation to rat striatal synaptosomes with a calculated IC 50 of 1.3 × 10 −6 M. Among DA uptake blockers some are known to act as DA releasing agents. Here we found that the DA uptake blocker nomifensine (30 μM) is unable to modify the baseline release of 3 H‐DA, whereas bupropion (10 μM) clearly elevates the baseline release of 3 H‐DA in a Ca 2+ ‐independent and Cl − ‐dependent manner. The non releasing agent nomifensine blocks the release of 3 H‐DA induced by bupropion. The Ca 2+ ‐dependent, high K + depolarization evoked release of 3 H‐DA is not modified by nomifensine and does not depend on the external Cl − concentration. When the depolarizing medium contains DA the carrier mediated release of 3 H‐DA induced by the external DA is additive to the high K + induced response. A drastic drop in the external Cl − concentration induces 3 H‐DA release. This release of 3 H‐DA induced by low external Cl − levels is completely blocked by nomifensine, which only slightly diminished the release of 3 H‐DA induced by the absence of external Na + . On the basis of these results, it is concluded that: (1) Rapid perfusion flow rates eliminate DA reuptake. (2) DA uptake inhibitors either with or without DA releasing capabilities block the release of DA induced by μM levels of external DA. (3) By preventing translocation of the DA transporter mobile moiety, nomifensine may inhibit the release of DA induced by external DA or bupropion and by drastic drops in the external Cl − w concentration. (4) In the absence of nomifensine, the DA transporter works under both resting and depolarized conditions, but in contrast to the GABA transporter (Sitges et al.: Neurochem Res 18:1081–1087, 1993), the DA transporter does not contribute to the amount of the DA released by depolarization. (5) Reversal of the DA uptake carrier is favored by conditions increasing the internal DA levels. (6) Cl − rather than Na + is a major determinant in 3 H‐DA movements through the DA transporter. Copyright © 1994 Wiley‐Liss, Inc.