Title | ARPP-21, a cAMP-regulated phosphoprotein enriched in dopamine-innervated brain regions: tissue distribution and regulation of phosphorylation in rat brain. |
Publication Type | Journal Article |
Year of Publication | 1990 |
Authors | Girault JA, Walaas SI, Hemmings HC, Greengard P |
Journal | Neuroscience |
Volume | 37 |
Issue | 2 |
Pagination | 317-25 |
Date Published | 1990 |
ISSN | 0306-4522 |
Keywords | 8-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 Journal | Neuroscience |
PubMed ID | 1966823 |
Grant List | MH-40899 / MH / NIMH NIH HHS / United States |