PT  - JOURNAL ARTICLE
AU  - Lana Kantor
AU  - G. H. Keikilani Hewlett
AU  - Yang Hae Park
AU  - Sarah M. Richardson-Burns
AU  - Mathew J. Mellon
AU  - Margaret E. Gnegy
TI  - Protein Kinase C and Intracellular Calcium Are Required for Amphetamine-Mediated Dopamine Release via the Norepinephrine Transporter in Undifferentiated PC12 Cells
DP  - 2001 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1016--1024
VI  - 297
IP  - 3
4099  - http://jpet.aspetjournals.org/content/297/3/1016.short
4100  - http://jpet.aspetjournals.org/content/297/3/1016.full
SO  - J Pharmacol Exp Ther2001 Jun 01; 297
AB  - The role of protein kinase C and intracellular Ca2+ 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 μM amphetamine. Direct activation of protein kinase C increased dopamine release in a Ca2+-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 Ca2+ 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 [3H]dopamine uptake. To more completely examine a role for Ca2+, intracellular Ca2+ was chelated in the cells. Depletion of intracellular Ca2+ considerably decreased dopamine release in response to 1 μM amphetamine compared with vehicle-treated cells, but had no effect on the [3H]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 Ca2+. Furthermore, protein kinase C and intracellular Ca2+ appear to regulate [3H]dopamine inward transport and amphetamine-mediated outward transport of dopamine independently in PC12 cells. The American Society for Pharmacology and Experimental Therapeutics