The responsiveness of the endogenous inhibitor of cAMP-dependent protein kinase to apomorphine in rat striatum after prolonged treatment with nomifensin.
Apomorphine produced biphasic changes in the activity of an endogenous, specific inhibitor of cAMP-dependent protein kinase (type I inhibitor). Small doses of apomorphine (50-100 micrograms/kg) induced an increase while high doses (1-10 mg/kg) produced a dose-dependent decrease of the type I inhibitor activity in the striatum of control rats. Prolonged treatment with nomifensin markedly reduced the response of the type I inhibitor both to low and high doses of apomorphine and shifted the dose-response curves to the right. The apomorphine-induced increase of the type I inhibitor activity in nomifensin-pretreated rats was blocked by aminophylline and by small, presynaptically active doses of haloperidol. This suggests that small doses of apomorphine stimulate presynaptic D2 receptor. The apomorphine-induced decrease of the type I inhibitor activity in nomifensin pretreated animals was enhanced by aminophylline and by presynaptically active dose of haloperidol. In contrast, this action of apomorphine was blocked by high, postsynaptically active, dose of haloperidol. It suggested postsynaptic site of action of high doses of apomorphine. Prolonged pretreatment with nomifensin resulted in subsensitivity of both presynaptic D2 and postsynaptic D1 receptors.
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009627:Nomifensine / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013569:Synapses / Q000378:metabolism
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011954:Receptors, Dopamine; C015482:protein kinase modulator; D009627:Nomifensine; D000628:Aminophylline; D006220:Haloperidol; D001058:Apomorphine