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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Apr;85(7):2407–2411. doi: 10.1073/pnas.85.7.2407

Desensitization of rat renal thick ascending limb cells to vasopressin.

J M Elalouf 1, D C Sari 1, N Roinel 1, C de Rouffignac 1
PMCID: PMC280002  PMID: 3353389

Abstract

Previous studies from this laboratory have demonstrated that vasopressin stimulates K, Mg, Ca, Cl, and Na reabsorption by the thick ascending limb of Henle's loop (TALH) of the rat kidney. Micropuncture of superficial nephrons and clearance experiments were performed to determine whether desensitization of the TALH to vasopressin may be demonstrated in vivo and whether such desensitization is specific for the effects of vasopressin (i.e., homologous) or also alters the response to the other hormones acting on the same pool of adenylate cyclase in this nephron segment. Brattleboro rats, with hereditary hypothalamic diabetes insipidus (DI), were given i.m. injections of 1-desamino-8-D-arginine-vasopressin (des-1-amino-[DArg8]VP (herein designated dDAVP); 2 micrograms/day) for 3 days. The effects of maximal physiological doses of arginine-8-vasopressin ([Arg8]VP (herein designated AVP); 20 pg/min per 100 g of body weight) were studied 2 days after the cessation of treatment, when the animals had returned to DI. The K, Mg, Ca, and, to a lesser extent, Cl and Na concentrations in the fluid leaving the TALH of superficial nephrons were higher in dDAVP-treated than in untreated rats given similar amounts of AVP during the experiments. A 50-60% desensitization of the TALH to AVP was still apparent 2 days after stopping the dDAVP injections. Desensitization is homologous, as judged from normal responses to physiological doses of glucagon and calcitonin, two hormones acting on the same cyclase pool as AVP in the rat TALH. The AVP-dependent increase of urine osmolality, however, indicated that its effects on the permeability to water of the collecting duct were scarcely affected in dDAVP-treated rats. It is concluded that (i) AVP induces homologous desensitization in the rat TALH and (ii) the TALH can be markedly desensitized to AVP when the collecting duct response to this hormone is poorly affected or even fully maintained.

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Selected References

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

  1. Baddouri K., Butlen D., Imbert-Teboul M., Le Bouffant F., Marchetti J., Chabardès D., Morel F. Plasma antidiuretic hormone levels and kidney responsiveness to vasopressin in the jerboa, Jaculus orientalis. Gen Comp Endocrinol. 1984 May;54(2):203–215. doi: 10.1016/0016-6480(84)90174-6. [DOI] [PubMed] [Google Scholar]
  2. Bailly C., Roinel N., Amiel C. PTH-like glucagon stimulation of Ca and Mg reabsorption in Henle's loop of the rat. Am J Physiol. 1984 Feb;246(2 Pt 2):F205–F212. doi: 10.1152/ajprenal.1984.246.2.F205. [DOI] [PubMed] [Google Scholar]
  3. Bouby N., Bankir L., Trinh-Trang-Tan M. M., Minuth W. W., Kriz W. Selective ADH-induced hypertrophy of the medullary thick ascending limb in Brattleboro rats. Kidney Int. 1985 Sep;28(3):456–466. doi: 10.1038/ki.1985.152. [DOI] [PubMed] [Google Scholar]
  4. Butlen D., Baddouri K., Rajerison R. M., Guillon G., Cantau B., Jard S. Plasma antidiuretic hormone levels and liver vasopressin receptors in the jerboa, Jaculus orientalis, and rat. Gen Comp Endocrinol. 1984 May;54(2):216–229. doi: 10.1016/0016-6480(84)90175-8. [DOI] [PubMed] [Google Scholar]
  5. Butlen D., Guillon G., Rajerison R. M., Jard S., Sawyer W. H., Manning M. Structural requirements for activation of vasopressin-sensitive adenylate cyclase, hormone binding, and antidiuretic actions: effects of highly potent analogues and competitive inhibitors. Mol Pharmacol. 1978 Nov;14(6):1006–1017. [PubMed] [Google Scholar]
  6. Di Stefano A., Elalouf J. M., Garel J. M., de Rouffignac C. Modulation by calcitonin of magnesium and calcium urinary excretion in the rat. Kidney Int. 1985 Feb;27(2):394–400. doi: 10.1038/ki.1985.22. [DOI] [PubMed] [Google Scholar]
  7. Doss R. C., Perkins J. P., Harden T. K. Recovery of beta-adrenergic receptors following long term exposure of astrocytoma cells to catecholamine. Role of protein synthesis. J Biol Chem. 1981 Dec 10;256(23):12281–12286. [PubMed] [Google Scholar]
  8. Elalouf J. M., Chabane Sari D., Roinel N., de Rouffignac C. NaCl and Ca delivery at the bend of rat deep nephrons decreases during antidiuresis. Am J Physiol. 1987 Jun;252(6 Pt 2):F1055–F1064. doi: 10.1152/ajprenal.1987.252.6.F1055. [DOI] [PubMed] [Google Scholar]
  9. Elalouf J. M., Di Stefano A., de Rouffignac C. Sensitivities of rat kidney thick ascending limbs and collecting ducts to vasopressin in vivo. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2276–2280. doi: 10.1073/pnas.83.7.2276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Elalouf J. M., Roinel N., de Rouffignac C. ADH-like effects of calcitonin on electrolyte transport by Henle's loop of rat kidney. Am J Physiol. 1984 Feb;246(2 Pt 2):F213–F220. doi: 10.1152/ajprenal.1984.246.2.F213. [DOI] [PubMed] [Google Scholar]
  11. Elalouf J. M., Roinel N., de Rouffignac C. Effects of antidiuretic hormone on electrolyte reabsorption and secretion in distal tubules of rat kidney. Pflugers Arch. 1984 Jun;401(2):167–173. doi: 10.1007/BF00583877. [DOI] [PubMed] [Google Scholar]
  12. Gellai M., Silverstein J. H., Hwang J. C., LaRochelle F. T., Jr, Valtin H. Influence of vasopressin on renal hemodynamics in conscious Brattleboro rats. Am J Physiol. 1984 Jun;246(6 Pt 2):F819–F827. doi: 10.1152/ajprenal.1984.246.6.F819. [DOI] [PubMed] [Google Scholar]
  13. Handler J. S., Preston A. S. Vasopressin-elicited refractoriness of the response to vasopressin in toad urinary bladder. Am J Physiol. 1981 Jun;240(6):F551–F557. doi: 10.1152/ajprenal.1981.240.6.F551. [DOI] [PubMed] [Google Scholar]
  14. Hsueh A. J., Dufau M. L., Catt K. J. Gonadotropin-induced regulation of luteinizing hormone receptors and desensitization of testicular 3':5'-cyclic AMP and testosterone responses. Proc Natl Acad Sci U S A. 1977 Feb;74(2):592–595. doi: 10.1073/pnas.74.2.592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Imbert-Teboul M., Chabardès D., Montégut M., Clique A., Morel F. Vasopressin-dependent adenylate cyclase activities in the rat kidney medulla: evidence for two separate sites of action. Endocrinology. 1978 Apr;102(4):1254–1261. doi: 10.1210/endo-102-4-1254. [DOI] [PubMed] [Google Scholar]
  16. Levy M., Starr N. L. The mechanism of glucagon-induced natriuresis in dogs. Kidney Int. 1972 Aug;2(2):76–84. doi: 10.1038/ki.1972.74. [DOI] [PubMed] [Google Scholar]
  17. Manning M., Balaspiri L., Moehring J., Haldar J., Sawyer W. H. Synthesis and some pharmacological properties of deamino(4-threonine,8-D-arginine)vasopressin and deamino(8-D-arginine)vasopressin, highly potent and specific antidiuretic peptides, and (8-D-arginine)vasopressin and deamino-arginine-vasopressin. J Med Chem. 1976 Jun;19(6):842–845. doi: 10.1021/jm00228a023. [DOI] [PubMed] [Google Scholar]
  18. Morel F., Chabardès D., Imbert-Teboul M., Le Bouffant F., Hus-Citharel A., Montégut M. Multiple hormonal control of adenylate cyclase in distal segments of the rat kidney. Kidney Int Suppl. 1982 May;11:S55–S62. [PubMed] [Google Scholar]
  19. Morel F., Imbert-Teboul M., Chabardès D. Receptors to vasopressin and other hormones in the mammalian kidney. Kidney Int. 1987 Feb;31(2):512–520. doi: 10.1038/ki.1987.30. [DOI] [PubMed] [Google Scholar]
  20. Rajerison R. M., Butlen D., Jard S. Effects of in vivo treatment with vasopressin and analogues on renal adenylate cyclase responsiveness to vasopressin stimulation in vitro. Endocrinology. 1977 Jul;101(1):1–12. doi: 10.1210/endo-101-1-1. [DOI] [PubMed] [Google Scholar]
  21. Rajerison R. M., Butlen D., Jard S. Ontogenic development of antidiuretic hormone receptors in rat kidney: comparison of hormonal binding and adenylate cyclase activation. Mol Cell Endocrinol. 1976 Mar;4(4):271–285. doi: 10.1016/0303-7207(76)90061-7. [DOI] [PubMed] [Google Scholar]
  22. Sasaki S., Imai M. Effects of vasopressin on water and NaCl transport across the in vitro perfused medullary thick ascending limb of Henle's loop of mouse, rat, and rabbit kidneys. Pflugers Arch. 1980 Feb;383(3):215–221. doi: 10.1007/BF00587521. [DOI] [PubMed] [Google Scholar]
  23. Sibley D. R., Lefkowitz R. J. Molecular mechanisms of receptor desensitization using the beta-adrenergic receptor-coupled adenylate cyclase system as a model. Nature. 1985 Sep 12;317(6033):124–129. doi: 10.1038/317124a0. [DOI] [PubMed] [Google Scholar]
  24. Su Y. F., Harden T. K., Perkins J. P. Catecholamine-specific desensitization of adenylate cyclase. Evidence for a multistep process. J Biol Chem. 1980 Aug 10;255(15):7410–7419. [PubMed] [Google Scholar]
  25. VALTIN H., SCHROEDER H. A., BENIRSCHKE K., SOKOL H. W. Familial hypothalamic diabetes insipidus in rats. Nature. 1962 Dec 15;196:1109–1110. doi: 10.1038/1961109a0. [DOI] [PubMed] [Google Scholar]
  26. Work J., Galla J. H., Booker B. B., Schafer J. A., Luke R. G. Effect of ADH on chloride reabsorption in the loop of Henle of the Brattleboro rat. Am J Physiol. 1985 Nov;249(5 Pt 2):F698–F703. doi: 10.1152/ajprenal.1985.249.5.F698. [DOI] [PubMed] [Google Scholar]
  27. de Rouffignac C., Corman B., Roinel N. Stimulation by antidiuretic hormone of electrolyte tubular reabsorption in rat kidney. Am J Physiol. 1983 Feb;244(2):F156–F164. doi: 10.1152/ajprenal.1983.244.2.F156. [DOI] [PubMed] [Google Scholar]

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