Differential modulation of the renal proximal tubular DA-1 receptor by Gpp(NH)p and sodium in the spontaneously hypertensive rat

J Auton Pharmacol. 1990:10 Suppl 1:s61-5. doi: 10.1111/j.1474-8673.1990.tb00229.x.

Abstract

1. In the normotensive rat (WKY) the guanine nucleotide, Gpp(NH)p, and sodium reduced the ability of the dopaminergic agonist fenoldopam to compete for the [3H]-SKF-38393 (dopamine-1 agonist) binding to the renal proximal tubular DA-1 receptors. 2. In the spontaneously hypertensive rat (SHR) Gpp(NH)p failed to reduce the affinity of fenoldopam for [3H]-SKF-38393 binding to renal tubular DA-1 receptors. 3. Sodium reduced the affinity of fenoldopam for [3H]-SKF-38393 binding in the SHR renal proximal tubular cells, but to a lesser extent than the WKY. 4. We conclude that the SHR has a defective DA-1 receptor or Gs/receptor coupling which interferes with the ability of Gpp(NH)p to act on the DA receptor/G protein complex.

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / analogs & derivatives
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / metabolism
  • Animals
  • Dopamine Agents / metabolism
  • Fenoldopam
  • Guanylyl Imidodiphosphate / pharmacology
  • Hypertension / metabolism*
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism*
  • Male
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D1
  • Sodium / pharmacology

Substances

  • Dopamine Agents
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Guanylyl Imidodiphosphate
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Sodium
  • Fenoldopam