RT Journal Article
SR Electronic
T1 Protein Kinase C and Intracellular Calcium Are Required for Amphetamine-Mediated Dopamine Release via the Norepinephrine Transporter in Undifferentiated PC12 Cells
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1016
OP 1024
VO 297
IS 3
A1 Lana Kantor
A1 G. H. Keikilani Hewlett
A1 Yang Hae Park
A1 Sarah M. Richardson-Burns
A1 Mathew J. Mellon
A1 Margaret E. Gnegy
YR 2001
UL http://jpet.aspetjournals.org/content/297/3/1016.abstract
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