Substrate-dependent regulation of MAO-A in rat mesangial cells: involvement of dopamine D2-like receptors

Am J Physiol Renal Physiol. 2003 Jan;284(1):F167-74. doi: 10.1152/ajprenal.00113.2002. Epub 2002 Sep 3.

Abstract

In the present study, we investigated the existence of a back-regulation of the catecholamine-degrading enzyme monoamine oxidase (MAO)-A by dopamine in rat renal cells. In proximal tubule cells, MAO-A expression was not modified after dopamine receptor stimulation. In contrast, in mesangial cells, enzyme assay and Western blots showed that MAO activity and protein increased by approximately 80% after 48-h incubation with the D(2)-like receptor agonist bromocriptine and quinpirole but not with the D(1)-like receptor agonist SKF-38393. This effect was prevented by the D(2)-receptor antagonist sulpiride and domperidone. The increase in MAO-A protein was preceded by an augmentation of MAO-A mRNA that was prevented by the transcriptional inhibitor actinomycin D. Bromocriptine effect was mimicked by the PKA inhibitor H89 and inhibited by the PKA activator 8-bromo-cAMP. These results show for the first time the existence of a dopamine-dependent MAO-A regulation involving D(2)-like receptors, inhibition of the cAMP-PKA pathway, and an ex novo enzyme synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / metabolism
  • Animals
  • Bromocriptine / pharmacology
  • Cells, Cultured
  • Dopamine / pharmacology
  • Dopamine Agonists / pharmacology
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / physiology
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / enzymology*
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / enzymology
  • Monoamine Oxidase / genetics*
  • Monoamine Oxidase / metabolism*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / metabolism*
  • Substrate Specificity

Substances

  • Adenylyl Cyclase Inhibitors
  • Dopamine Agonists
  • RNA, Messenger
  • Receptors, Dopamine D2
  • Bromocriptine
  • Monoamine Oxidase
  • Adenylyl Cyclases
  • Dopamine