Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1983 May;79(1):313–321. doi: 10.1111/j.1476-5381.1983.tb10526.x

Characterization and partial purification of 'renocortins': two polypeptides formed in renal cells causing the anti-phospholipase-like action of glucocorticoids.

J F Cloix, O Colard, B Rothhut, F Russo-Marie
PMCID: PMC2044833  PMID: 6575852

Abstract

1 Anti-inflammatory steroids reduce prostaglandin E2 (PGE2) synthesis in rat renomedullary interstitial cells in culture by inhibiting the release of arachidonic acid from membranous phospholipid stores, exhibiting antiphospholipase-like properties. 2 After treatment of the cells with dexamethasone 10(-6)M, these cells release a protein in the supernatant. 3 This supernatant is able to inhibit PGE2 secretion in untreated cells and to inhibit phospholipase A2 activity in an in vitro system. 4 Using chromatofocusing separation, we showed that two distinct proteins exist with isoelectric points of 5.8 and 8.3. 5 Using gel permeation separation, we showed that two proteins exist with apparent molecular weights of 15,000 and 30,000 daltons. 6 We conclude that, in renal cells in culture, anti-inflammatory steroids induce the synthesis and the release of two polypeptides which we have named 'Renocortins' (induced by corticoids in renal cells) causing the antiphospholipase-like action of glucocorticoids. 7 Our results are in good agreement with others, but as renal cells are not directly involved in the inflammatory process, we suggest that this steroid-induced phenomenon is not solely involved in the inflammatory reaction but is of more general physiological relevance.

Full text

PDF
313

Selected References

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

  1. Blackwell G. J., Carnuccio R., Di Rosa M., Flower R. J., Langham C. S., Parente L., Persico P., Russel-Smith N. C., Stone D. Glucocorticoids induce the formation and release of anti-inflammatory and anti-phospholipase proteins into the peritoneal cavity of the rat. Br J Pharmacol. 1982 May;76(1):185–194. doi: 10.1111/j.1476-5381.1982.tb09205.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blackwell G. J., Carnuccio R., Di Rosa M., Flower R. J., Parente L., Persico P. Macrocortin: a polypeptide causing the anti-phospholipase effect of glucocorticoids. Nature. 1980 Sep 11;287(5778):147–149. doi: 10.1038/287147a0. [DOI] [PubMed] [Google Scholar]
  3. Blackwell G. J., Flower R. J., Nijkamp F. P., Vane J. R. Phospholipase A2 activity of guinea-pig isolated perfused lungs: stimulation, and inhibition by anti-inflammatory steroids. Br J Pharmacol. 1978 Jan;62(1):79–89. doi: 10.1111/j.1476-5381.1978.tb07009.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bonilla C. A., Dupont J. Fatty acid and prostaglandin composition of left ventricular myocardium from dexamethasone-treated dogs with severe low output syndrome (LOS). Prostaglandins. 1976 Jun;11(6):935–951. doi: 10.1016/0090-6980(76)90003-4. [DOI] [PubMed] [Google Scholar]
  5. Carnuccio R., Di Rosa M., Persico P. Hydrocortisone-induced inhibitor of prostaglandin biosynthesis in rat leucocytes. Br J Pharmacol. 1980 Jan;68(1):14–16. doi: 10.1111/j.1476-5381.1980.tb10691.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Danon A., Assouline G. Inhibition of prostaglandin biosynthesis by corticosteroids requires RNA and protein synthesis. Nature. 1978 Jun 15;273(5663):552–554. doi: 10.1038/273552a0. [DOI] [PubMed] [Google Scholar]
  7. Floman Y., Zor U. Mechanism of steroid action in inflammation: inhibition of prostaglandin synthesis and release. Prostaglandins. 1976 Sep;12(3):403–413. doi: 10.1016/0090-6980(76)90021-6. [DOI] [PubMed] [Google Scholar]
  8. Flower R. J., Blackwell G. J. Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation. Nature. 1979 Mar 29;278(5703):456–459. doi: 10.1038/278456a0. [DOI] [PubMed] [Google Scholar]
  9. Gryglewski R. J., Panczenko B., Korbut R., Grodzinska L., Ocetkiewicz A. Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pig. Prostaglandins. 1975 Aug;10(2):343–355. doi: 10.1016/0090-6980(75)90053-2. [DOI] [PubMed] [Google Scholar]
  10. Hirata F., Schiffmann E., Venkatasubramanian K., Salomon D., Axelrod J. A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids. Proc Natl Acad Sci U S A. 1980 May;77(5):2533–2536. doi: 10.1073/pnas.77.5.2533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hirata F., del Carmine R., Nelson C. A., Axelrod J., Schiffmann E., Warabi A., De Blas A. L., Nirenberg M., Manganiello V., Vaughan M. Presence of autoantibody for phospholipase inhibitory protein, lipomodulin, in patients with rheumatic diseases. Proc Natl Acad Sci U S A. 1981 May;78(5):3190–3194. doi: 10.1073/pnas.78.5.3190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hong S. L., Levine L. Inhibition of arachidonic acid release from cells as the biochemical action of anti-inflammatory corticosteroids. Proc Natl Acad Sci U S A. 1976 May;73(5):1730–1734. doi: 10.1073/pnas.73.5.1730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kantrowitz F., Robinson D. R., McGuire M. B., Levine L. Corticosteroids inhibit prostaglandin production by rheumatiod synovia. Nature. 1975 Dec 25;258(5537):737–739. doi: 10.1038/258737a0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Moore P. K., Hoult J. R. Anti-inflammatory steroids reduce tissue PG synthetase activity and enhance PG breakdown. Nature. 1980 Nov 20;288(5788):269–270. doi: 10.1038/288269a0. [DOI] [PubMed] [Google Scholar]
  16. Muirhead E. E., Germain G., Leach B. E., Pitcock J. A., Stephenson P., Brooks B., Brosius W. L., Daniels E. G., Hinman J. W. Production of renomedullary prostaglandins by renomedullary interstitial cells grown in tissue culture. Circ Res. 1972 Sep;31(9 Suppl):161–172. [PubMed] [Google Scholar]
  17. Newcombe D. S., Fahey J. V., Ishikawa Y. Hydrocortisone inhibition of the bradykinin activation of human synovial fibroblasts. Prostaglandins. 1977 Feb;13(2):235–244. doi: 10.1016/0090-6980(77)90005-3. [DOI] [PubMed] [Google Scholar]
  18. Nijkamp F. P., Flower R. J., Moncada S., Vane J. R. Partial purification of rabbit aorta contracting substance-releasing factor and inhibition of its activity by anti-inflammatory steroids. Nature. 1976 Oct 7;263(5577):479–482. doi: 10.1038/263479a0. [DOI] [PubMed] [Google Scholar]
  19. Parente L., Ammendola G., Persico P., di Rosa M. Glucocorticosteroids, prostaglandins and the inflammatory process. Pol J Pharmacol Pharm. 1978 Mar-Jun;30(2-3):141–155. [PubMed] [Google Scholar]
  20. Russo-Marie F., Duval D. Dexamethasone-induced inhibition of prostaglandin production dose not result from a direct action on phospholipase activities but is mediated through a steroid-inducible factor. Biochim Biophys Acta. 1982 Jul 20;712(1):177–185. doi: 10.1016/0005-2760(82)90100-x. [DOI] [PubMed] [Google Scholar]
  21. Russo-Marie F., Paing M., Duval D. Involvement of glucocorticoid receptors in steroid-induced inhibition of prostaglandin secretion. J Biol Chem. 1979 Sep 10;254(17):8498–8504. [PubMed] [Google Scholar]
  22. Russo-Marie F., Seillan C., Duval D. Effect of dexamethasone on cyclo-oxygenase activity in reno-medullary cells in culture. Agents Actions. 1980 Dec;10(6):516–519. doi: 10.1007/BF02024155. [DOI] [PubMed] [Google Scholar]
  23. Saeed S. A., McDonald-Gibson W. J., Cuthbert J., Copas J. L., Schneider C., Gardiner P. J., Butt N. M., Collier H. O. Endogenous inhibitor of prostaglandin synthetase. Nature. 1977 Nov 3;270(5632):32–36. doi: 10.1038/270032a0. [DOI] [PubMed] [Google Scholar]
  24. Tashjian A. H., Jr, Voelkel E. F., McDonough J., Levine L. Hydrocortisone inhibits prostaglandin production by mouse fibrosarcoma cells. Nature. 1975 Dec 25;258(5537):739–741. doi: 10.1038/258739a0. [DOI] [PubMed] [Google Scholar]
  25. Tsurufuji S., Sugio K., Takemasa F. The role of glucocorticoid receptor and gene expression in the anti-inflammatory action of dexamethasone. Nature. 1979 Aug 2;280(5721):408–410. doi: 10.1038/280408a0. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES