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. 1980;300:105–114. doi: 10.1113/jphysiol.1980.sp013154

Separate and combined effects of ouabain and extracellular potassium on renin secretion from rat renal cortical slices

Monique C Churchill 1, Paul C Churchill 1
PMCID: PMC1279347  PMID: 6991669

Abstract

1. Renin secretion of rat renal cortical slices was measured as a function of extracellular K and ouabain concentrations in the incubation medium.

2. A sigmoid relationship was found between renin secretion and log K concentration over the range 1·0-4·0 mM. Secretion was maximal at about 2·25 mM-K and half-maximal at about 1·43 mM-K.

3. In media containing 4·0 mM-K, ouabain at 10-8, 10-7, and 10-6 M did not affect renin secretion. Higher concentrations of ouabain inhibited secretion. A sigmoid relationship was found between% inhibition of secretion and log ouabain concentration (10-6-10-3 M). Inhibition was half-maximal at 2·3 × 10-5 M and complete at 10-3 M-ouabain.

4. Lowering extracellular K concentration from 4·0 to 2·25 mM shifted the dose-effect curve of ouabain to the left. At 2·25 mM-K, inhibition of renin secretion was half-maximal at 10-5 M-ouabain.

5. The inhibitory effect of 2 × 10-5 M-ouabain (twice the dose for 50% inhibition) in media containing 2·25 mM-K was nearly identical to the combined effect of lowering K to 1·43 mM (the concentration required for 50% inhibition) and adding 10-5 M-ouabain. This observation suggests that ouabain and low extracellular K act at a common site, presumably on Na, K-ATPase activity, to inhibit renin secretion.

6. Neither 10-3 M-ouabain nor K-free medium inhibited renin secretion when the concentration of free Ca in the medium was lowered to < 10-8 M. Therefore it is proposed that as a result of Na, K-ATPase inhibition, (a) intracellular Na increases, (b) intracellular Ca increases via Na-Ca exchange, provided that extracellular Ca exceeds 10-8 M, and that (c) Ca accumulation, in some unknown manner, inhibits renin secretion from rat renal cortical slices.

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Selected References

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

  1. Akera T., Brody T. M. The role of Na+,K+-ATPase in the inotropic action of digitalis. Pharmacol Rev. 1977 Sep;29(3):187–220. [PubMed] [Google Scholar]
  2. Barajas L. Renin secretion: an anatomical basis for tubular control. Science. 1971 Apr 30;172(3982):485–487. doi: 10.1126/science.172.3982.485. [DOI] [PubMed] [Google Scholar]
  3. Baumbach L., Leyssac P. P., Skinner S. L. Studies on renin release from isolated superfused glomeruli: effects of temperature, urea, ouabain and ethacrynic acid. J Physiol. 1976 Jun;258(1):243–256. doi: 10.1113/jphysiol.1976.sp011417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baumbach L., Leyssac P. P. Studies on the mechanism of renin release from isolated superfused rat glomeruli: effects of calcium, calcium ionophore and lanthanum. J Physiol. 1977 Dec;273(3):745–764. doi: 10.1113/jphysiol.1977.sp012121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blaine E. H., Zimmerman M. B. Renal function and renin secretion after administration of ouabain and ouabain plus furosemide in conscious sheep. Circ Res. 1978 Jul;43(1):36–43. doi: 10.1161/01.res.43.1.36. [DOI] [PubMed] [Google Scholar]
  6. Blaustein M. P. The interrelationship between sodium and calcium fluxes across cell membranes. Rev Physiol Biochem Pharmacol. 1974;70:33–82. doi: 10.1007/BFb0034293. [DOI] [PubMed] [Google Scholar]
  7. Churchill P. C., McDonald F. D. Effect of ouabain on renin secretion in anaesthetized dogs. J Physiol. 1974 Nov;242(3):635–646. doi: 10.1113/jphysiol.1974.sp010727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Churchill P. C. Possible mechanism of the inhibitory effect of ouabain on renin secretion from rat renal cortical slices. J Physiol. 1979 Sep;294:123–134. doi: 10.1113/jphysiol.1979.sp012919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DUNHAM E. T., GLYNN I. M. Adenosinetriphosphatase activity and the active movements of alkali metal ions. J Physiol. 1961 Apr;156:274–293. doi: 10.1113/jphysiol.1961.sp006675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fleckenstein A. Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Annu Rev Pharmacol Toxicol. 1977;17:149–166. doi: 10.1146/annurev.pa.17.040177.001053. [DOI] [PubMed] [Google Scholar]
  11. Fynn M., Onomakpome N., Peart W. S. The effects of ionophores (A23187 and RO2-2985) on renin secretion and renal vasoconstriction. Proc R Soc Lond B Biol Sci. 1977 Nov 14;199(1135):199–212. doi: 10.1098/rspb.1977.0135. [DOI] [PubMed] [Google Scholar]
  12. Haulica I., Petrescu G., Branisteanu D., Rosca V., Balan G. Recherches sur le rôle des phénomènes membranaires dans la sécrétion de la rénine. J Physiol (Paris) 1974 Mar;68(1):17–26. [PubMed] [Google Scholar]
  13. Hokin L. E. Purification and properties of the (sodium + potassium)-activated adenosinetriphosphatase and reconstitution of sodium transport. Ann N Y Acad Sci. 1974;242(0):12–23. doi: 10.1111/j.1749-6632.1974.tb19075.x. [DOI] [PubMed] [Google Scholar]
  14. Lee K. S., Klaus W. The subcellular basis for the mechanism of inotropic action of cardiac glycosides. Pharmacol Rev. 1971 Sep;23(3):193–261. [PubMed] [Google Scholar]
  15. Lyons H. J., Chruchhill P. C. Renin secretion from rat renal cortical cell suspensions. Am J Physiol. 1975 Jun;228(6):1835–1839. doi: 10.1152/ajplegacy.1975.228.6.1835. [DOI] [PubMed] [Google Scholar]
  16. Lyons H. J., Churchill P. C. The influence of ouabain on in vitro renin secretion and intracellular sodium. Nephron. 1975;14(6):442–450. doi: 10.1159/000180478. [DOI] [PubMed] [Google Scholar]
  17. Lyons H. J., Churchill P. C. The influence of ouabain on in vitro renin secretion. Proc Soc Exp Biol Med. 1974 Apr;145(4):1148–1150. doi: 10.3181/00379727-145-37970. [DOI] [PubMed] [Google Scholar]
  18. MCCLANE T. K. A BIPHASIC ACTION OF OUABAIN ON SODIUM TRANSPORT IN THE TOAD BLADDER. J Pharmacol Exp Ther. 1965 Apr;148:106–110. [PubMed] [Google Scholar]
  19. Morris B. J., Johnston C. I. Isolation of renin granules from rat kidney cortex and evidence for an inactive form of renin (prorenin) in granules and plasma. Endocrinology. 1976 Jun;98(6):1466–1474. doi: 10.1210/endo-98-6-1466. [DOI] [PubMed] [Google Scholar]
  20. PALMER R. F., NECHAY B. R. BIPHASIC RENAL EFFECTS OF OUABAIN IN THE CHICKEN: CORRELATION WITH A MICROSOMAL NA+-K+ STIMULATED ATP-ASE. J Pharmacol Exp Ther. 1964 Oct;146:92–98. [PubMed] [Google Scholar]
  21. Park C. S., Malvin R. L. Calcium in the control of renin release. Am J Physiol. 1978 Jul;235(1):F22–F25. doi: 10.1152/ajprenal.1978.235.1.F22. [DOI] [PubMed] [Google Scholar]
  22. Robinson J. D. Cation interactions with different functional states of the Na+, K+-ATPase. Ann N Y Acad Sci. 1974;242(0):185–202. doi: 10.1111/j.1749-6632.1974.tb19090.x. [DOI] [PubMed] [Google Scholar]
  23. Rubin R. P. The role of calcium in the release of neurotransmitter substances and hormones. Pharmacol Rev. 1970 Sep;22(3):389–428. [PubMed] [Google Scholar]
  24. Van Dongen R., Peart W. S. Calcium dependence of the inhibitory effect of angiotensin on renin secretion in the isolated perfused kidney of the rat. Br J Pharmacol. 1974 Jan;50(1):125–129. doi: 10.1111/j.1476-5381.1974.tb09599.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Vander A. J. Control of renin release. Physiol Rev. 1967 Jul;47(3):359–382. doi: 10.1152/physrev.1967.47.3.359. [DOI] [PubMed] [Google Scholar]
  26. Whittam R., Ager M. E. Vectorial aspects of adenosine-triphosphatase activity in erythrocyte membranes. Biochem J. 1964 Nov;93(2):337–348. doi: 10.1042/bj0930337. [DOI] [PMC free article] [PubMed] [Google Scholar]

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