Inhibition of Na+,K(+)-ATPase in rat renal proximal tubules by dopamine involved DA-1 receptor activation

Naunyn Schmiedebergs Arch Pharmacol. 1993 Mar;347(3):289-95. doi: 10.1007/BF00167447.

Abstract

Endogenous kidney dopamine (DA) causes natriuresis and diuresis, at least partly, via inhibition of proximal tubular Na+,K(+)-ATPase. The present study was done to identify the dopamine receptor subtype(s) involved in dopamine-induced inhibition of Na+,K(+)-ATPase activity. Suspensions of renal proximal tubules from Sprague-Dawley rats were incubated with dopamine, the DA-1 receptor agonist fenoldopam or the DA-2 receptor agonist SK&F 89124 in the presence or absence of either the DA-1 receptor antagonist SCH 23390 or the DA-2 receptor antagonist domperidone. Dopamine and fenoldopam (10(-5) to 10(-8) mol/l) produced a concentration-dependent inhibition of Na+,K(+)-ATPase activity. However, SK&F 89124 failed to produce any significant effect over the same concentration range. Incubation with fenoldopam (10(-5) to 10(-8) mol/l) in the presence of SK&F 89124 (10(-6) mol/l) inhibited Na+,K(+)-ATPase activity to a degree similar to that with fenoldopam alone. Furthermore, DA-induced inhibition of Na+,K(+)-ATPase activity was attenuated by SCH 23390, but not by domperidone. Since alpha-adrenoceptor activation is reported to stimulate Na+,K(+)-ATPase activity and, at higher concentrations, dopamine also acts as an alpha-adrenoceptor agonist, the potential opposing effect from alpha-adrenoceptor activation on DA-induced inhibition of Na+,K(+)-ATPase activity was investigated by using the alpha-adrenoceptor blocker phentolamine. We found that, in the lower concentration range (10(-5) to 10(-7) mol/l), dopamine-induced inhibition of Na+,K(+)-ATPase activity in the presence of phentolamine was similar in magnitude to that observed with dopamine alone.(ABSTRACT TRUNCATED AT 250 WORDS)

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 / pharmacology
  • Animals
  • Benzazepines / pharmacology
  • Centrifugation, Density Gradient
  • Dopamine / pharmacology*
  • Dopamine Agents / pharmacology
  • Dopamine Antagonists
  • Fenoldopam
  • In Vitro Techniques
  • Indoles / pharmacology
  • Kidney Tubules, Proximal / enzymology*
  • Male
  • Nystatin / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / drug effects
  • Receptors, Dopamine D1 / physiology*
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors*

Substances

  • Benzazepines
  • Dopamine Agents
  • Dopamine Antagonists
  • Indoles
  • Receptors, Dopamine D1
  • Nystatin
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • SK&F 89124
  • Sodium-Potassium-Exchanging ATPase
  • Fenoldopam
  • Dopamine