Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1989 Dec;84(6):1849–1856. doi: 10.1172/JCI114371

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

S Kinoshita 1, A Sidhu 1, R A Felder 1
PMCID: PMC304064  PMID: 2574187

Abstract

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.

Full text

PDF
1851

Images in this article

1854Image
on p.1854
1854Image
on p.1854

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bello-Reuss E., Higashi Y., Kaneda Y. Dopamine decreases fluid reabsorption in straight portions of rabbit proximal tubule. Am J Physiol. 1982 Jun;242(6):F634–F640. doi: 10.1152/ajprenal.1982.242.6.F634. [DOI] [PubMed] [Google Scholar]
  2. Bertorello A., Aperia A. Both DA1 and DA2 receptor agonists are necessary to inhibit NaKATPase activity in proximal tubules from rat kidney. Acta Physiol Scand. 1988 Mar;132(3):441–443. doi: 10.1111/j.1748-1716.1988.tb08350.x. [DOI] [PubMed] [Google Scholar]
  3. Bertorello A., Aperia A. Na+-K+-ATPase is an effector protein for protein kinase C in renal proximal tubule cells. Am J Physiol. 1989 Feb;256(2 Pt 2):F370–F373. doi: 10.1152/ajprenal.1989.256.2.F370. [DOI] [PubMed] [Google Scholar]
  4. Bertorello A., Hökfelt T., Goldstein M., Aperia A. Proximal tubule Na+-K+-ATPase activity is inhibited during high-salt diet: evidence for DA-mediated effect. Am J Physiol. 1988 Jun;254(6 Pt 2):F795–F801. doi: 10.1152/ajprenal.1988.254.6.F795. [DOI] [PubMed] [Google Scholar]
  5. Biollaz J., Waeber B., Diezi J., Burnier M., Brunner H. R. Lithium infusion to study sodium handling in unanesthetized hypertensive rats. Hypertension. 1986 Feb;8(2):117–121. doi: 10.1161/01.hyp.8.2.117. [DOI] [PubMed] [Google Scholar]
  6. Burant C. F., Lemmon S. K., Treutelaar M. K., Buse M. G. Insulin resistance of denervated rat muscle: a model for impaired receptor-function coupling. Am J Physiol. 1984 Nov;247(5 Pt 1):E657–E666. doi: 10.1152/ajpendo.1984.247.5.E657. [DOI] [PubMed] [Google Scholar]
  7. Carey R. M., Stote R. M., Dubb J. W., Townsend L. H., Rose C. E., Jr, Kaiser D. L. Selective peripheral dopamine-1 receptor stimulation with fenoldopam in human essential hypertension. J Clin Invest. 1984 Dec;74(6):2198–2207. doi: 10.1172/JCI111646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dilley J. R., Stier C. T., Jr, Arendshorst W. J. Abnormalities in glomerular function in rats developing spontaneous hypertension. Am J Physiol. 1984 Jan;246(1 Pt 2):F12–F20. doi: 10.1152/ajprenal.1984.246.1.F12. [DOI] [PubMed] [Google Scholar]
  9. Felder R. A., Blecher M., Calcagno P. L., Jose P. A. Dopamine receptors in the proximal tubule of the rabbit. Am J Physiol. 1984 Sep;247(3 Pt 2):F499–F505. doi: 10.1152/ajprenal.1984.247.3.F499. [DOI] [PubMed] [Google Scholar]
  10. Felder R. A., Jose P. A. Dopamine1 receptors in rat kidneys identified with 125I-Sch 23982. Am J Physiol. 1988 Nov;255(5 Pt 2):F970–F976. doi: 10.1152/ajprenal.1988.255.5.F970. [DOI] [PubMed] [Google Scholar]
  11. Felder R. A., Seikaly M. G., Eisner G. M., Jose P. A. Renal dopamine-1 defect in spontaneous hypertension. Contrib Nephrol. 1988;67:71–74. doi: 10.1159/000415377. [DOI] [PubMed] [Google Scholar]
  12. Fernandez-Pardal J., Saavedra J. M. Catecholamines in discrete kidney regions. Changes in salt-sensitive Dahl hypertensive rats. Hypertension. 1982 Nov-Dec;4(6):821–826. doi: 10.1161/01.hyp.4.6.821. [DOI] [PubMed] [Google Scholar]
  13. Garg L. C., Narang N., McArdle S. Na-K-ATPase in nephron segments of rats developing spontaneous hypertension. Am J Physiol. 1985 Dec;249(6 Pt 2):F863–F869. doi: 10.1152/ajprenal.1985.249.6.F863. [DOI] [PubMed] [Google Scholar]
  14. Haga T., Ross E. M., Anderson H. J., Gilman A. G. Adenylate cyclase permanently uncoupled from hormone receptors in a novel variant of S49 mouse lymphoma cells. Proc Natl Acad Sci U S A. 1977 May;74(5):2016–2020. doi: 10.1073/pnas.74.5.2016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hagege J., Richet G. Proximal tubule dopamine histofluorescence in renal slices incubated with L-dopa. Kidney Int. 1985 Jan;27(1):3–8. doi: 10.1038/ki.1985.2. [DOI] [PubMed] [Google Scholar]
  16. Hansell P., Ande'n N. E., Grabowska-Ande'n M., Ulfendahl H. R. Atrial natriuretic factor, urinary catechol compounds and electrolyte excretion in rats during normal hydration and isotonic volume expansion. Influence of dopamine receptor blockade. Acta Physiol Scand. 1988 Nov;134(3):421–428. doi: 10.1111/j.1748-1716.1988.tb08510.x. [DOI] [PubMed] [Google Scholar]
  17. Jeffrey R. F., Macdonald T. M., Brown J., Rae P. W., Lee M. R. The effect of lithium on the renal response to the dopamine prodrug gludopa in normal man. Br J Clin Pharmacol. 1988 Jun;25(6):725–732. doi: 10.1111/j.1365-2125.1988.tb05259.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jose P. A., Felder R. A., Holloway R. R., Eisner G. M. Dopamine receptors modulate sodium excretion in denervated kidney. Am J Physiol. 1986 Jun;250(6 Pt 2):F1033–F1038. doi: 10.1152/ajprenal.1986.250.6.F1033. [DOI] [PubMed] [Google Scholar]
  19. Kikuchi K., Iimura O., Yamaji I., Shibata S., Nishimura M., Aoki K., Nozawa A., Hasegawa T., Honma C., Kobayakawa H. The pathophysiological role of water-sodium balance and renal dopaminergic activity in overweight patients with essential hypertension. J Clin Hypertens. 1987 Mar;3(1):3–11. [PubMed] [Google Scholar]
  20. Kuchel O., Racz K., Debinski W., Falardeau P., Buu N. T. Contrasting dopaminergic patterns in two forms of genetic hypertension. Clin Exp Hypertens A. 1987;9(5-6):987–1008. doi: 10.3109/10641968709161461. [DOI] [PubMed] [Google Scholar]
  21. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  22. Morel F., Doucet A. Hormonal control of kidney functions at the cell level. Physiol Rev. 1986 Apr;66(2):377–468. doi: 10.1152/physrev.1986.66.2.377. [DOI] [PubMed] [Google Scholar]
  23. Muto S., Tabei K., Asano Y., Imai M. Dopaminergic inhibition of the action of vasopressin on the cortical collecting tubule. Eur J Pharmacol. 1985 Aug 27;114(3):393–397. doi: 10.1016/0014-2999(85)90386-3. [DOI] [PubMed] [Google Scholar]
  24. Niznik H. B., Jarvie K. R., Bzowej N. H., Seeman P., Garlick R. K., Miller J. J., Jr, Baindur N., Neumeyer J. L. Photoaffinity labeling of dopamine D1 receptors. Biochemistry. 1988 Oct 4;27(20):7594–7599. doi: 10.1021/bi00420a004. [DOI] [PubMed] [Google Scholar]
  25. Parenti P., Hanozet G. M., Bianchi G. Sodium and glucose transport across renal brush border membranes of Milan hypertensive rats. Hypertension. 1986 Oct;8(10):932–939. doi: 10.1161/01.hyp.8.10.932. [DOI] [PubMed] [Google Scholar]
  26. Pelayo J. C., Fildes R. D., Eisner G. M., Jose P. A. Effects of dopamine blockade on renal sodium excretion. Am J Physiol. 1983 Aug;245(2):F247–F253. doi: 10.1152/ajprenal.1983.245.2.F247. [DOI] [PubMed] [Google Scholar]
  27. Racz K., Kuchel O., Buu N. T. Abnormal adrenal catecholamine synthesis in salt-sensitive Dahl rats. Hypertension. 1987 Jan;9(1):76–80. doi: 10.1161/01.hyp.9.1.76. [DOI] [PubMed] [Google Scholar]
  28. Richet G., Wahbe F., Hagège J., Wiemeyer W. Extraneuronal production of dopamine by kidney slices in normo and hypertensive rats. Clin Exp Hypertens A. 1987;9 (Suppl 1):127–134. doi: 10.3109/10641968709160169. [DOI] [PubMed] [Google Scholar]
  29. Roos J. C., Kirchner K. A., Abernethy J. D., Langford H. G. Differential effect of salt loading on sodium and lithium excretion in Dahl salt-resistant and -sensitive rats. Hypertension. 1984 May-Jun;6(3):420–424. doi: 10.1161/01.hyp.6.3.420. [DOI] [PubMed] [Google Scholar]
  30. Rubalcava B., Rodbell M. The role of acidic phospholipids in glucagon action on rat liver adenylate cyclase. J Biol Chem. 1973 Jun 10;248(11):3831–3837. [PubMed] [Google Scholar]
  31. Saito I., Takeshita E., Saruta T., Nagano S., Sekihara T. Urinary dopamine excretion in normotensive subjects with or without family history of hypertension. J Hypertens. 1986 Feb;4(1):57–60. doi: 10.1097/00004872-198602000-00009. [DOI] [PubMed] [Google Scholar]
  32. Seri I., Kone B. C., Gullans S. R., Aperia A., Brenner B. M., Ballermann B. J. Locally formed dopamine inhibits Na+-K+-ATPase activity in rat renal cortical tubule cells. Am J Physiol. 1988 Oct;255(4 Pt 2):F666–F673. doi: 10.1152/ajprenal.1988.255.4.F666. [DOI] [PubMed] [Google Scholar]
  33. Setler P. E., Sarau H. M., Zirkle C. L., Saunders H. L. The central effects of a novel dopamine agonist. Eur J Pharmacol. 1978 Aug 15;50(4):419–430. doi: 10.1016/0014-2999(78)90148-6. [DOI] [PubMed] [Google Scholar]
  34. Siragy H. M., Felder R. A., Howell N. L., Chevalier R. L., Peach M. J., Carey R. M. Evidence that intrarenal dopamine acts as a paracrine substance at the renal tubule. Am J Physiol. 1989 Sep;257(3 Pt 2):F469–F477. doi: 10.1152/ajprenal.1989.257.3.F469. [DOI] [PubMed] [Google Scholar]
  35. Spiegel A. M., Levine M. A., Aurbach G. D., Downs R. W., Jr, Marx S. J., Lasker R. D., Moses A. M., Breslau N. A. Deficiency of hormone receptor-adenylate cyclase coupling protein: basis for hormone resistance in pseudohypoparathyroidism. Am J Physiol. 1982 Jul;243(1):E37–E42. doi: 10.1152/ajpendo.1982.243.1.E37. [DOI] [PubMed] [Google Scholar]
  36. Srinivasan K., Awapara J. Substrate specificity and other properties of DOPA decarboxylase from guinea pig kidneys. Biochim Biophys Acta. 1978 Oct 12;526(2):597–604. doi: 10.1016/0005-2744(78)90150-x. [DOI] [PubMed] [Google Scholar]
  37. Stote R. M., Dubb J. W., Familiar R. G., Erb B. B., Alexander F. A new oral renal vasodilator, fenoldopam. Clin Pharmacol Ther. 1983 Sep;34(3):309–315. doi: 10.1038/clpt.1983.173. [DOI] [PubMed] [Google Scholar]
  38. Yoshimura M., Kambara S., Okabayashi H., Ikegaiki I., Matsuzawa M., Suga K., Takahashi H., Ijichi H. Pathophysiological role of dopamine on the development of hypertension in rats. Jpn Circ J. 1987 Oct;51(10):1226–1231. doi: 10.1253/jcj.51.1226. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES