Dopamine causes stimulation of protein kinase C in rat renal proximal tubules by activating dopamine D1 receptors

Eur J Pharmacol. 1995 Apr 28;289(2):391-4. doi: 10.1016/0922-4106(95)90119-1.


Although it is suggested that in the renal proximal tubules, dopamine D1 receptor activation causes inhibition of Na+/K+ATPase via a phospholipase C and protein kinase C coupled pathway, the direct stimulation of protein kinase C by dopamine has not been reported. The present study was designed to examine the effects of dopamine and selective dopamine D1 receptor and dopamine D2 receptor agonists on protein kinase C activity. The renal proximal tubule suspensions were obtained from male Sprague-Dawley rats. The tubules were incubated separately with dopamine and fenoldopam in the presence or absence of dopamine D1 receptor antagonist, SCH 23390 ([(R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine]). The protein kinase C activity was measured by using a kinase target peptide, conjugated to a fluorescent molecule in water. The amino acid sequence of this peptide is, Proline-Leucine-Serine-Arginine-Threonine-Leucine-Serine-Valine-Alanine- Alanine-Lysine(PKSRTLSVAAK). We found that dopamine and fenoldopam [6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepine-7,8-di ol] produced concentration-dependent increases in protein kinase C activity, which was blocked by SCH 23390. However, the dopamine D2 receptor agonist, bromocriptine [(5' alpha)-2-bromo-12'-hydroxy-2'-(1-methyl-ethyl)-5'-(2-methylpropyl)erg o- taman-3',6',18-trione] failed to stimulate protein kinase C activity at all the concentrations tested. These results provide direct evidence that dopamine stimulates protein kinase C activity via activation of dopamine D1 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bromocriptine / pharmacology
  • Dopamine / pharmacology*
  • Dose-Response Relationship, Drug
  • Fenoldopam / pharmacology
  • Kidney / drug effects*
  • Male
  • Protein Kinase C / drug effects
  • Protein Kinase C / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / drug effects*


  • Receptors, Dopamine D1
  • Bromocriptine
  • Protein Kinase C
  • Fenoldopam
  • Dopamine