Protein kinase C and dopamine release--III. Effect of dopamine depleting drugs

The hypothesis that protein kinase C (PKC) may modulate the release of dopamine (DA) in the nigrostriatal pathway was supported by findings that injections of drugs which affect DA release in vivo result in changes in PKC activity in the striatum (Giambalvo CT, Biochem Pharmacol 37: 4009-4017, 1988). In the present study, it was found that the effects of the DA-acting drugs (apomorphine, LY 171555, SKF 38393, sulpiride, Sch 23390 and gamma-butyrolactone) on PKC activity were prevented by prior diminution of the endogenous stores of DA with alpha-methyl-p-tyrosine (alpha-MT) or reserpine. This protective effect occurred at a dose and time when DA depletion was maximal, suggesting that the effects of the DA-acting drugs on PKC activity are dependent on the presence of an intact store of DA. Furthermore, since reserpine decreased the evoked release of DA, these results raise the possibility that PKC may be involved in the vesicular release process. Besides their effects on PKC activity, these depleting agents also prevented the DA-acting drugs from altering calmodulin-dependent protein kinase activity.