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

Neuroscience. 1990;37(2):317-25. doi: 10.1016/0306-4522(90)90402-p.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Animals
  • Brain Chemistry / physiology*
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / metabolism
  • Cyclic AMP / physiology*
  • Dopamine / physiology*
  • In Vitro Techniques
  • Male
  • Nerve Tissue Proteins / physiology*
  • Neurons / drug effects
  • Neurons / physiology
  • Phosphoproteins / physiology*
  • Phosphorylation
  • Putamen / drug effects
  • Putamen / metabolism
  • Quinolinic Acid
  • Quinolinic Acids / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Substantia Nigra / drug effects
  • Substantia Nigra / physiology


  • Nerve Tissue Proteins
  • Phosphoproteins
  • Quinolinic Acids
  • cyclic AMP-regulated phosphoprotein ARPP-21
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Cyclic AMP
  • Quinolinic Acid
  • Dopamine