Defective dopamine-1 receptor adenylate cyclase coupling in the proximal convoluted tubule from the spontaneously hypertensive rat

J Clin Invest. 1989 Dec;84(6):1849-56. doi: 10.1172/JCI114371.


The natriuretic effect of DA-1 agonists is less in the spontaneously hypertensive rat (SHR) than its normotensive control, the Wistar-Kyoto rat (WKY). To determine a mechanism of the decreased effect of DA-1 agonists on sodium transport, DA-1 receptors in renal proximal convoluted tubule (PCT) were studied by radioligand binding and by adenylate cyclase (AC) determinations. Specific binding of 125I-SCH 23982 (defined by 10 microM SCH 23390, a DA-1 antagonist) was concentration dependent, saturable, and stereoselective. The dissociation constant, maximum receptor density, and DA-1 antagonist inhibition constant were similar in SHR and WKY. The apparent molecular weight of the DA-1 receptor determined by the photoaffinity D1 probe 125I-MAB was also similar in WKY and SHR. However, DA-1 agonists competed more effectively for specific 125I-SCH 23982 binding sites in WKY than in SHR. Basal as well as forskolin, parathyroid hormone, GTP and Gpp(NH)p-stimulated-AC activities were similar. In contrast DA-1 agonists (fenoldopam, SKF 38393, SND 911C12) stimulated AC activity to a lesser extent in SHR. GTP and Gpp(NH)p enhanced the ability of DA-1 agonists to stimulate AC activity in WKY but not in SHR. These data suggest a defect in the DA-1 receptor-second messenger coupling mechanism in the PCT of the SHR.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

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
  • Adenylyl Cyclases / metabolism*
  • Affinity Labels
  • Animals
  • Benzazepines* / analogs & derivatives*
  • Benzazepines* / metabolism
  • Binding, Competitive
  • Dopamine Agents / metabolism
  • Dopamine Agents / pharmacology
  • Dopamine Antagonists
  • Fenoldopam
  • Guanine Nucleotides / pharmacology
  • Hypertension / metabolism*
  • Kidney Tubules, Proximal / metabolism*
  • Male
  • Molecular Weight
  • Photochemistry
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D1


  • 8-iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol
  • Affinity Labels
  • Benzazepines
  • Dopamine Agents
  • Dopamine Antagonists
  • Guanine Nucleotides
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Adenylyl Cyclases
  • Fenoldopam