PROTEIN-KINASE-C ACTIVATORS DECREASE DOPAMINE UPTAKE INTO STRIATAL SYNAPTOSOMES

Incubation with either of the protein kinase C activators phorbol 12-m yristate 13-acetate (PMA) and sn-1,2 dioctanoylglycerol (DiC(8)) decre ased the uptake of dopamine into striatal synaptosomes, whereas the in active 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 i n the K-m. Neither PMA nor DiC(8) affected mazindol binding to the dop amine transporter. Preincubation with the protein kinase inhibitor sta urosporine prevented the DiC(8)-induced decrease of dopamine uptake. F urthermore, the protein phosphatase inhibitor okadaic acid decreased d opamine uptake by itself and enhanced the DiC(8)-induced reduction of uptake. These findings support a role for protein kinase C in modulati ng dopamine transporter activity.