Protein kinase C and intracellular calcium are required for amphetamine-mediated dopamine release via the norepinephrine transporter in undifferentiated PC12 cells.
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Kantor L, Hewlett GH, Park YH, Richardson-Burns SM, Mellon MJ, Gnegy ME
Protein kinase C and intracellular calcium are required for amphetamine-mediated dopamine release via the norepinephrine transporter in undifferentiated PC12 cells.
J Pharmacol Exp Ther. 2001 Jun;297(3):1016-24.
- PubMed ID
- 11356924 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Imipramine Sodium-dependent noradrenaline transporter Protein Humans YesInhibitorDetails