In vivo modulation of striatal phosphoproteins by dopaminergic agents.
Protein phosphorylation in the brain represents a common target for several second messenger systems. A phosphoprotein (DARPP-32) specifically regulated by cAMP and dopamine has been detected in neurons bearing dopamine D-1 receptors, where it plays a key role in eliciting cAMP-mediated intracellular responses. The endogenous phosphorylation of this cytosolic protein is markedly affected after in vivo acute treatment with the selective D-1 agonist, SKF 38393. The amount of the DARPP-32 dephospho-form measured by a back-phosphorylation assay was decreased by about 30% in agonist-treated animals. This effect was completely counteracted by the concomitant administration of the selective D-1 antagonist, SCH 23390, but not by a selective D-2 antagonist. This first demonstration of in vivo modulation of the phosphorylation state of DARPP-32 could, as a biochemical approach, represent a useful tool to gain further insight into the cascade of biochemical events elicited by specific dopaminergic drugs.
Di Luca
M
M
Institute of Pharmacological Sciences, University of Milan, Italy.
Cimino
M
M
Abbracchio
M P
MP
Cattabeni
F
F
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism* / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004591:Electrophoresis, Polyacrylamide Gel; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007525:Isoelectric Focusing; D008297:Male; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D014020:Tissue Extracts / Q000494:pharmacology
D015259:Dopamine Agents; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D014020:Tissue Extracts; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D010744:Phosphoric Monoester Hydrolases