The effect of stimulation of pre- and postsynaptic dopamine receptors on the endogenous inhibitor of cAMP-dependent protein kinase.

The effect of various doses of apomorphine on the activity of specific endogenous inhibitor of cAMP dependent protein kinase (type I inhibitor) was studied. Apomorphine produced biphasic changes in the type I inhibitor activity in rat striatum. Small doses (50-100 micrograms/kg) induced an increase while large doses (0.5-10 mg/kg) caused a dose dependent decrease of the type I inhibitor activity. The apomorphine induced increase in type I inhibitor activity was completely blocked by small, presynaptically active doses of haloperidol and chlorpromazine and by aminophylline. This suggests that small doses of apomorphine stimulate presynaptic dopamine D2-receptors. In contrast, the apomorphine induced decrease of the type I inhibitor activity was greatly potentiated by aminophylline and by presynaptically active doses of the neuroleptics, suggesting a postsynaptic site of action for large doses of apomorphine. Determination of the type I inhibitor activity is proposed as one of the biochemical tests allowing to recognize the site of action of drugs stimulating dopamine receptors.