Department of Anesthesiology

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ARPP-21, a cAMP-regulated phosphoprotein enriched in dopamine-innervated brain regions: tissue distribution and regulation of phosphorylation in rat brain.

TitleARPP-21, a cAMP-regulated phosphoprotein enriched in dopamine-innervated brain regions: tissue distribution and regulation of phosphorylation in rat brain.
Publication TypeJournal Article
Year of Publication1990
AuthorsGirault JA, Walaas SI, Hemmings HC, Greengard P
JournalNeuroscience
Volume37
Issue2
Pagination317-25
Date Published1990
ISSN0306-4522
Keywords8-Bromo Cyclic Adenosine Monophosphate, Animals, Brain Chemistry, Caudate Nucleus, Cyclic AMP, Dopamine, Male, Nerve Tissue Proteins, Neurons, Phosphoproteins, Phosphorylation, Putamen, Quinolinic Acid, Quinolinic Acids, Rats, Rats, Inbred Strains, Substantia Nigra
Abstract

ARPP-21 (cAMP-regulated phosphoprotein, Mr = 21,000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate), a phosphoprotein substrate for cAMP-dependent protein kinase, is unevenly distributed in adult rat brain. Using immunoblotting and phosphorylation in vitro followed by immunoprecipitation, ARPP-21 was found to be enriched in caudate-putamen, substantia nigra, nucleus accumbens and olfactory tubercle. Intermediate levels were found in cerebral cortex and hippocampus. ARPP-21 was very low in most other brain areas and was not detected in any of the peripheral tissues studied. Following unilateral lesion of the caudate-putamen with quinolinic acid, a marked decrease in the levels of ARPP-21 was observed in both the lesioned caudate-putamen (-75%) and the ipsilateral substantia nigra (-70%) compared with the unlesioned side. This result demonstrates the enrichment of ARPP-21 in striatonigral neurons. In slices of caudate-putamen, substantia nigra or cerebral cortex incubated in vitro, the phosphorylation of ARPP-21 was enhanced by 8-Br-cAMP, a stable analog of cAMP. In striatal slices, forskolin, a compound which stimulates adenylate cyclase directly, enhanced the phosphorylation of ARPP-21 with an EC50 of 0.5 microM. In conclusion, ARPP-21 is a neuron-specific phosphoprotein enriched in specific brain areas which are known to receive a rich dopaminergic innervation and to contain high levels of D1 dopamine receptors. The phosphorylation of ARPP-21 is likely to mediate some of the intracellular effects of neurotransmitters which stimulate adenylate cyclase in these regions, in particular dopamine and vasoactive intestinal peptide.

Alternate JournalNeuroscience
PubMed ID1966823
Grant ListMH-40899 / MH / NIMH NIH HHS / United States