Alterations in dopamine DA1 receptor and G proteins in renal proximal tubules of old rats

Am J Physiol. 1997 Jul;273(1 Pt 2):F53-9. doi: 10.1152/ajprenal.1997.273.1.F53.

Abstract

The present study examines the effect of dopamine DA1-receptor agonists on the renal proximal tubular Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity and quantitates DA1 receptors and the coupled G proteins in Fischer 344 model of adult (6 mo old) and old (23 mo old) rats. Dopamine and the preferential DA1-receptor agonist, SKF-38393, produced a concentration-dependent inhibition of Na(+)-K(+)-ATPase activity in proximal tubules from adult rats, whereas the enzyme activity was unaffected by these agonists in the old rats. The binding of DA1-receptor antagonist [3H]Sch-23390 in the proximal tubular basolateral membranes showed a marked decrease (approximately 47%) in the receptor numbers in old compared with adult rats, whereas dissociation constant (Kd) values in old compared with adult rats were not significantly different. Dopamine and SKF-38393 stimulated 35S-labeled guanosine 5'-O-(3-thiotriphosphate) binding in adult rats, but there was no significant effect on the binding in the old rats. Quantification of G2 alpha and Gq/11 alpha using Western analysis revealed a significant increase in quantities of both the G proteins in old rats. The data suggest that a reduction in DA1 receptor number and subsequently reduced G protein activation may be the causative factors for the impairment in DA1 receptor-mediated inhibition of Na(+)-K(+)-ATPase activity in the proximal tubules of old rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Aging / physiology*
  • Animals
  • Benzazepines / metabolism
  • Blood Pressure
  • Cell Membrane / metabolism
  • Dopamine / pharmacology*
  • Dopamine Agonists / pharmacology*
  • GTP-Binding Proteins / metabolism*
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Heart Rate
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / growth & development
  • Kidney Tubules, Proximal / metabolism*
  • Kinetics
  • Male
  • Rats
  • Rats, Inbred F344
  • Receptors, Dopamine D1 / metabolism*
  • Regression Analysis
  • Sodium-Potassium-Exchanging ATPase / drug effects
  • Sodium-Potassium-Exchanging ATPase / metabolism*

Substances

  • Benzazepines
  • Dopamine Agonists
  • Receptors, Dopamine D1
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • GTP-Binding Proteins
  • Sodium-Potassium-Exchanging ATPase
  • Dopamine