Localization of cyclic GMP-dependent protein kinase in rat basal ganglia neurons.
Cyclic GMP-dependent protein kinase displays an uneven distribution in brain, being highly concentrated only in cerebellar Purkinje cells. Using DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein, Mr 32,000) as exogenous substrate, and performing assays in the absence or presence of the protein inhibitor of cyclic AMP-dependent protein kinase, we have now identified both cyclic AMP-dependent and cyclic GMP-dependent protein kinase activities in the rat neostriatum and substantia nigra. Quinolinic acid-induced degeneration of neostriatal neurons and the straitonigral fibers emanating from neostriatal neurons decreased the activities of both cyclic nucleotide-dependent enzymes by 70-85% in the neostriatum, while cyclic GMP-dependent protein kinase was decreased by 44% and cyclic AMP-dependent protein kinase was decreased by 18% in the substantia nigra. In the basal ganglia, cyclic GMP-dependent protein kinase therefore appears enriched in striatonigral neurons, while cyclic AMP-dependent protein kinase is present both in striatonigral neurons and in other cells. The results indicate that cyclic GMP-regulated protein phosphorylation may play a role in the function of distinct basal ganglion neurons.
Walaas
S I
SI
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021.
Girault
J A
JA
Greengard
P
P
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001479:Basal Ganglia / Q000201:enzymology*; D003292:Convulsants / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D011494:Protein Kinases / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology
D003292:Convulsants; D011725:Pyridines; D011805:Quinolinic Acids; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D011494:Protein Kinases; D017378:Quinolinic Acid; D006152:Cyclic GMP