Protein kinase C activators decrease dopamine uptake into striatal synaptosomes
Copeland, B.J.; Vogelsberg, V.; Neff, N.H.; Hadjiconstantinou, M.
Journal of Pharmacology and Experimental Therapeutics 277(3): 1527-1532
1996
ISSN/ISBN: 0022-3565 PMID: 8667219 Document Number: 468143
Incubation with either of the protein kinase C activators phorbol 12-myristate 13-acetate (PMA) and sn-1,2 dioctanoylglycerol (DiC-8) decreased the uptake of dopamine into striatal synaptosomes, whereas the inactive phorbol ester 4-alpha-PMA had no effect. Washout of PMA and DiC-8 failed to reverse the decrease in uptake. Kinetic analysis showed a decrease in the apparent V-max for the transporter without changes in the K-m. Neither PMA nor DiC-8 affected mazindol binding to the dopamine transporter. Preincubation with the protein kinase inhibitor staurosporine prevented the DiC-8-induced-decrease of dopamine uptake. Furthermore, the protein phosphatase inhibitor okadaic acid decreased dopamine uptake by itself and enhanced the DiC-8-induced reduction of uptake. These findings support a role for protein kinase C in modulating dopamine transporter activity.