Cooperation between D1- and D2-dopamine receptors in the nucleus accumbens.
Apomorphine, used in small doses (20-50 micrograms/kg), induced an increase in the activity of an endogenous inhibitor of cAMP dependent protein kinases (Walsh inhibitor, type I inhibitor) in nucleus accumbens of the rat. The action of apomorphine was blocked by sulpiride and aminophylline and enhanced by SCH-23390. Pretreatment with 6-OH-dopamine resulted in a shift of the dose-response curve for apomorphine to the left, suggesting supersensitivity of D2 receptors. Moreover, stimulation of D2 receptors induced a decrease in phosphorylation of DARPP-32, a specific protein, located in neurones containing D1 receptors. Large doses of apomorphine (over 0.5 mg/kg) provoked a decrease in type I inhibitor activity, blocked by SCH-23390 and enhanced by sulpiride and aminophylline. Moreover, SCH-23390 blocked a decrease in type I inhibitor activity induced by large doses of sulpiride and sulpiride blocked an increase in type I inhibitor activity produced by large doses of SCH-23390. The results suggest that D1 and D2 receptors in the nucleus accumbens could cooperate with the same adenylate cyclase and could be located on the same neurones.
Szmigielski
A
A
Department of Pharmacodynamics, Medical Academy, Lodz, Poland.
Zalewska-Kaszubska
J
J
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002352:Carrier Proteins / Q000187:drug effects; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D006892:Hydroxydopamines / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D002352:Carrier Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D006892:Hydroxydopamines; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C015482:protein kinase modulator; D013469:Sulpiride; D016627:Oxidopamine; D001058:Apomorphine