Inhibition of Cerebral Protein Kinase C in Vitro by Cocaine and Methamphetamine
Protein kinase C, which participates in cellular responses to various stimuli such as hormones, neurotransmitters and growth factors, is essential for cell proliferation and differentiation. Activation of the enzyme has been suggested to be important in neurotransmitter release, learning and memory, long-term potentiation, and cocaine-induced motor activity. Our previous study showed that monoamine uptake inhibitors imipramine and desipramine inhibited protein kinase C activity in a crude extract from the rat cerebral cortex. The present study examined the effect of cocaine and methamphetamine on activity of the soluble protein kinase C in a crude extract of the rat cerebral cortex. Cocaine and methamphetamine were found to inhibit protein kinase C in the soluble fraction at higher concentrations. It is, therefore, conceivable that the neural action of cocaine and methamphetamine may, at least in part, be associated with their inhibitory effect on protein kinase C.
