| Autor: |
Kantor L; Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA., Hewlett GH, Park YH, Richardson-Burns SM, Mellon MJ, Gnegy ME |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2001 Jun; Vol. 297 (3), pp. 1016-24. |
| Abstrakt: |
The role of protein kinase C and intracellular Ca(2+) on amphetamine-mediated dopamine release through the norepinephrine plasmalemmal transporter in undifferentiated PC12 cells was investigated. The selective protein kinase C inhibitor chelerythrine completely inhibited endogenous dopamine release elicited by 1 microM amphetamine. Direct activation of protein kinase C increased dopamine release in a Ca(2+)-insensitive, imipramine-sensitive manner and the release was not additive with amphetamine. Exocytosis was not involved since these events were not altered by either deletion of extracellular Ca(2+) or reserpine pretreatment. Down-regulation of protein kinase C activity by long-term phorbol ester treatment resulted in a dramatic decrease in amphetamine-mediated dopamine release with no apparent effect on [(3)H]dopamine uptake. To more completely examine a role for Ca(2+), intracellular Ca(2+) was chelated in the cells. Depletion of intracellular Ca(2+) considerably decreased dopamine release in response to 1 microM amphetamine compared with vehicle-treated cells, but had no effect on the [(3)H]dopamine uptake. Thus, our results suggest that amphetamine-mediated dopamine release through the plasmalemmal norepinephrine transporter is highly dependent on protein kinase C activity and intracellular but not extracellular Ca(2+). Furthermore, protein kinase C and intracellular Ca(2+) appear to regulate [(3)H]dopamine inward transport and amphetamine-mediated outward transport of dopamine independently in PC12 cells. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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