Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Apr 1;88(7):2798–2801. doi: 10.1073/pnas.88.7.2798

Phosphorylated Mr 32,000 dopamine- and cAMP-regulated phosphoprotein inhibits Na+,K(+)-ATPase activity in renal tubule cells.

A Aperia 1, J Fryckstedt 1, L Svensson 1, H C Hemmings Jr 1, A C Nairn 1, P Greengard 1
PMCID: PMC51326  PMID: 1849276

Abstract

Dopamine inhibits Na+,K(+)-ATPase activity in several renal tubule segments and thereby regulates urinary Na+ excretion. We now show that a phosphopeptide of 31 amino acids, corresponding to residues 8-38 of the protein phosphatase inhibitor DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32,000), mimics the inhibitory action of dopamine on Na+,K(+)-ATPase activity in renal tubule cells from the ascending limb of the loop of Henle. The dephosphorylated form of the peptide is ineffective. The results indicate that dopamine acts through a protein phosphorylation pathway to regulate the activity of an ion pump. In addition, the data suggest that inhibition of protein phosphatase 1 by phophorylated DARPP-32 is a component of the mechanism by which dopamine regulates urinary Na+ excretion.

Full text

PDF
2798

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aperia A., Bertorello A., Seri I. Dopamine causes inhibition of Na+-K+-ATPase activity in rat proximal convoluted tubule segments. Am J Physiol. 1987 Jan;252(1 Pt 2):F39–F45. doi: 10.1152/ajprenal.1987.252.1.F39. [DOI] [PubMed] [Google Scholar]
  2. Bertorello A. M., Hopfield J. F., Aperia A., Greengard P. Inhibition by dopamine of (Na(+)+K+)ATPase activity in neostriatal neurons through D1 and D2 dopamine receptor synergism. Nature. 1990 Sep 27;347(6291):386–388. doi: 10.1038/347386a0. [DOI] [PubMed] [Google Scholar]
  3. Bertorello A., Hökfelt T., Goldstein M., Aperia A. Proximal tubule Na+-K+-ATPase activity is inhibited during high-salt diet: evidence for DA-mediated effect. Am J Physiol. 1988 Jun;254(6 Pt 2):F795–F801. doi: 10.1152/ajprenal.1988.254.6.F795. [DOI] [PubMed] [Google Scholar]
  4. Epstein F. H. Hypoxia of the renal medulla. Q J Med. 1985 Dec;57(224):807–810. [PubMed] [Google Scholar]
  5. Felder R. A., Felder C. C., Eisner G. M., Jose P. A. The dopamine receptor in adult and maturing kidney. Am J Physiol. 1989 Sep;257(3 Pt 2):F315–F327. doi: 10.1152/ajprenal.1989.257.3.F315. [DOI] [PubMed] [Google Scholar]
  6. Halpain S., Girault J. A., Greengard P. Activation of NMDA receptors induces dephosphorylation of DARPP-32 in rat striatal slices. Nature. 1990 Jan 25;343(6256):369–372. doi: 10.1038/343369a0. [DOI] [PubMed] [Google Scholar]
  7. Hebert S. C., Andreoli T. E. Control of NaCl transport in the thick ascending limb. Am J Physiol. 1984 Jun;246(6 Pt 2):F745–F756. doi: 10.1152/ajprenal.1984.246.6.F745. [DOI] [PubMed] [Google Scholar]
  8. Hemmings H. C., Jr, Greengard P. DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein: regional, tissue, and phylogenetic distribution. J Neurosci. 1986 May;6(5):1469–1481. doi: 10.1523/JNEUROSCI.06-05-01469.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hemmings H. C., Jr, Greengard P., Tung H. Y., Cohen P. DARPP-32, a dopamine-regulated neuronal phosphoprotein, is a potent inhibitor of protein phosphatase-1. Nature. 1984 Aug 9;310(5977):503–505. doi: 10.1038/310503a0. [DOI] [PubMed] [Google Scholar]
  10. Hemmings H. C., Jr, Nairn A. C., Elliott J. I., Greengard P. Synthetic peptide analogs of DARPP-32 (Mr 32,000 dopamine- and cAMP-regulated phosphoprotein), an inhibitor of protein phosphatase-1. Phosphorylation, dephosphorylation, and inhibitory activity. J Biol Chem. 1990 Nov 25;265(33):20369–20376. [PubMed] [Google Scholar]
  11. Jørgensen P. L. Structure, function and regulation of Na,K-ATPase in the kidney. Kidney Int. 1986 Jan;29(1):10–20. doi: 10.1038/ki.1986.3. [DOI] [PubMed] [Google Scholar]
  12. Kaczmarek L. K., Jennings K. R., Strumwasser F., Nairn A. C., Walter U., Wilson F. D., Greengard P. Microinjection of catalytic subunit of cyclic AMP-dependent protein kinase enhances calcium action potentials of bag cell neurons in cell culture. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7487–7491. doi: 10.1073/pnas.77.12.7487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lee M. R. Dopamine and the kidney. Clin Sci (Lond) 1982 May;62(5):439–448. doi: 10.1042/cs0620439. [DOI] [PubMed] [Google Scholar]
  14. Meister B., Fryckstedt J., Schalling M., Cortés R., Hökfelt T., Aperia A., Hemmings H. C., Jr, Nairn A. C., Ehrlich M., Greengard P. Dopamine- and cAMP-regulated phosphoprotein (DARPP-32) and dopamine DA1 agonist-sensitive Na+,K+-ATPase in renal tubule cells. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8068–8072. doi: 10.1073/pnas.86.20.8068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ouimet C. C., Greengard P. Distribution of DARPP-32 in the basal ganglia: an electron microscopic study. J Neurocytol. 1990 Feb;19(1):39–52. doi: 10.1007/BF01188438. [DOI] [PubMed] [Google Scholar]
  16. Shenolikar S., Nairn A. C. Protein phosphatases: recent progress. Adv Second Messenger Phosphoprotein Res. 1991;23:1–121. [PubMed] [Google Scholar]
  17. Shyjan A. W., Ceña V., Klein D. C., Levenson R. Differential expression and enzymatic properties of the Na+,K(+)-ATPase alpha 3 isoenzyme in rat pineal glands. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1178–1182. doi: 10.1073/pnas.87.3.1178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Skou J. C. The Na,K-pump. Methods Enzymol. 1988;156:1–25. doi: 10.1016/0076-6879(88)56004-4. [DOI] [PubMed] [Google Scholar]
  19. Walaas S. I., Aswad D. W., Greengard P. A dopamine- and cyclic AMP-regulated phosphoprotein enriched in dopamine-innervated brain regions. Nature. 1983 Jan 6;301(5895):69–71. doi: 10.1038/301069a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES