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. 1989 Feb;83(2):708–712. doi: 10.1172/JCI113935

Endothelin stimulates phospholipase C, Na+/H+ exchange, c-fos expression, and mitogenesis in rat mesangial cells.

M S Simonson 1, S Wann 1, P Mené 1, G R Dubyak 1, M Kester 1, Y Nakazato 1, J R Sedor 1, M J Dunn 1
PMCID: PMC303732  PMID: 2536405

Abstract

A recently described peptide hormone, endothelin, is a potent vasoconstrictor, but it is unclear whether endothelin has other biological actions. These experiments extend the range of biological actions of endothelin to stimulation of mitogenesis. Endothelin at low concentrations (0.1-10 nM) induced mitogenesis by quiescent rat glomerular mesangial cells in culture. Mitogenesis induced by endothelin was accompanied by activation of phospholipase C with increased inositol phosphate turnover and increments of intracellular [Ca2+]. Endothelin also activated Na+/H+ exchange, causing cytosolic alkalinization, and enhanced transcription of the c-fos protooncogene, additional biochemical signals closely linked to proliferation. In addition to being a vasoconstrictor, endothelin thus also functions as a mitogen, presumably through activation of phospholipase C.

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Selected References

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  1. Berridge M. J. Inositol lipids and cell proliferation. Biochim Biophys Acta. 1987 Apr 20;907(1):33–45. doi: 10.1016/0304-419x(87)90017-5. [DOI] [PubMed] [Google Scholar]
  2. Berridge M. J. Inositol trisphosphate and diacylglycerol: two interacting second messengers. Annu Rev Biochem. 1987;56:159–193. doi: 10.1146/annurev.bi.56.070187.001111. [DOI] [PubMed] [Google Scholar]
  3. Bonventre J. V., Skorecki K. L., Kreisberg J. I., Cheung J. Y. Vasopressin increases cytosolic free calcium concentration in glomerular mesangial cells. Am J Physiol. 1986 Jul;251(1 Pt 2):F94–102. doi: 10.1152/ajprenal.1986.251.1.F94. [DOI] [PubMed] [Google Scholar]
  4. Brasaemle D. L., Attie A. D. Microelisa reader quantitation of fixed, stained, solubilized cells in microtitre dishes. Biotechniques. 1988 May;6(5):418–419. [PubMed] [Google Scholar]
  5. Dubyak G. R., De Young M. B. Intracellular Ca2+ mobilization activated by extracellular ATP in Ehrlich ascites tumor cells. J Biol Chem. 1985 Sep 5;260(19):10653–10661. [PubMed] [Google Scholar]
  6. Furchgott R. F. Role of endothelium in responses of vascular smooth muscle. Circ Res. 1983 Nov;53(5):557–573. doi: 10.1161/01.res.53.5.557. [DOI] [PubMed] [Google Scholar]
  7. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  8. Hawkins P. T., Stephens L., Downes C. P. Rapid formation of inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4-trisphosphate in rat parotid glands may both result indirectly from receptor-stimulated release of inositol 1,4,5-trisphosphate from phosphatidylinositol 4,5-bisphosphate. Biochem J. 1986 Sep 1;238(2):507–516. doi: 10.1042/bj2380507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hirata Y., Yoshimi H., Takata S., Watanabe T. X., Kumagai S., Nakajima K., Sakakibara S. Cellular mechanism of action by a novel vasoconstrictor endothelin in cultured rat vascular smooth muscle cells. Biochem Biophys Res Commun. 1988 Aug 15;154(3):868–875. doi: 10.1016/0006-291x(88)90220-3. [DOI] [PubMed] [Google Scholar]
  10. Holt J. T., Gopal T. V., Moulton A. D., Nienhuis A. W. Inducible production of c-fos antisense RNA inhibits 3T3 cell proliferation. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4794–4798. doi: 10.1073/pnas.83.13.4794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Itoh Y., Yanagisawa M., Ohkubo S., Kimura C., Kosaka T., Inoue A., Ishida N., Mitsui Y., Onda H., Fujino M. Cloning and sequence analysis of cDNA encoding the precursor of a human endothelium-derived vasoconstrictor peptide, endothelin: identity of human and porcine endothelin. FEBS Lett. 1988 Apr 25;231(2):440–444. doi: 10.1016/0014-5793(88)80867-6. [DOI] [PubMed] [Google Scholar]
  12. Jover E., Couraud F., Rochat H. Two types of scorpion neurotoxins characterized by their binding to two separate receptor sites on rat brain synaptosomes. Biochem Biophys Res Commun. 1980 Aug 29;95(4):1607–1614. doi: 10.1016/s0006-291x(80)80082-9. [DOI] [PubMed] [Google Scholar]
  13. Kester M., Menè P., Dubyak G. R., Dunn M. J. Elevation of cytosolic free calcium by platelet-activating factor in cultured rat mesangial cells. FASEB J. 1987 Sep;1(3):215–219. doi: 10.1096/fasebj.1.3.2442057. [DOI] [PubMed] [Google Scholar]
  14. Kremer S., Harper P., Hegele R., Skorecki K. Bradykinin stimulates a rise in cytosolic calcium in renal glomerular mesangial cells via a pertussis toxin insensitive pathway. Can J Physiol Pharmacol. 1988 Jan;66(1):43–48. doi: 10.1139/y88-008. [DOI] [PubMed] [Google Scholar]
  15. Majerus P. W., Connolly T. M., Deckmyn H., Ross T. S., Bross T. E., Ishii H., Bansal V. S., Wilson D. B. The metabolism of phosphoinositide-derived messenger molecules. Science. 1986 Dec 19;234(4783):1519–1526. doi: 10.1126/science.3024320. [DOI] [PubMed] [Google Scholar]
  16. Menè P., Abboud H. E., Dubyak G. R., Scarpa A., Dunn M. J. Effects of PDGF on inositol phosphates, Ca2+, and contraction of mesangial cells. Am J Physiol. 1987 Sep;253(3 Pt 2):F458–F463. doi: 10.1152/ajprenal.1987.253.3.F458. [DOI] [PubMed] [Google Scholar]
  17. Meyer T., Holowka D., Stryer L. Highly cooperative opening of calcium channels by inositol 1,4,5-trisphosphate. Science. 1988 Apr 29;240(4852):653–656. doi: 10.1126/science.2452482. [DOI] [PubMed] [Google Scholar]
  18. Moolenaar W. H. Effects of growth factors on intracellular pH regulation. Annu Rev Physiol. 1986;48:363–376. doi: 10.1146/annurev.ph.48.030186.002051. [DOI] [PubMed] [Google Scholar]
  19. Nilson J. H., Nejedlik M. T., Virgin J. B., Crowder M. E., Nett T. M. Expression of alpha subunit and luteinizing hormone beta genes in the ovine anterior pituitary. Estradiol suppresses accumulation of mRNAS for both alpha subunit and luteinizing hormone beta. J Biol Chem. 1983 Oct 25;258(20):12087–12090. [PubMed] [Google Scholar]
  20. Rink T. J., Tsien R. Y., Pozzan T. Cytoplasmic pH and free Mg2+ in lymphocytes. J Cell Biol. 1982 Oct;95(1):189–196. doi: 10.1083/jcb.95.1.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. doi: 10.1056/NEJM198602203140806. [DOI] [PubMed] [Google Scholar]
  22. Rozengurt E. Early signals in the mitogenic response. Science. 1986 Oct 10;234(4773):161–166. doi: 10.1126/science.3018928. [DOI] [PubMed] [Google Scholar]
  23. Scarpa A. Measurements of cation transport with metallochromic indicators. Methods Enzymol. 1979;56:301–338. doi: 10.1016/0076-6879(79)56030-3. [DOI] [PubMed] [Google Scholar]
  24. Schlondorff D. The glomerular mesangial cell: an expanding role for a specialized pericyte. FASEB J. 1987 Oct;1(4):272–281. doi: 10.1096/fasebj.1.4.3308611. [DOI] [PubMed] [Google Scholar]
  25. Schuldiner S., Rozengurt E. Na+/H+ antiport in Swiss 3T3 cells: mitogenic stimulation leads to cytoplasmic alkalinization. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7778–7782. doi: 10.1073/pnas.79.24.7778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Simonson M. S., Dunn M. J. Direct measurements of cell number using computer-aided video microscopy. Anal Biochem. 1987 Nov 15;167(1):106–112. doi: 10.1016/0003-2697(87)90138-2. [DOI] [PubMed] [Google Scholar]
  27. Simonson M. S., Mené P., Dubyak G. R., Dunn M. J. Identification and transmembrane signaling of leukotriene D4 receptors in human mesangial cells. Am J Physiol. 1988 Dec;255(6 Pt 1):C771–C780. doi: 10.1152/ajpcell.1988.255.6.C771. [DOI] [PubMed] [Google Scholar]
  28. Soltoff S. P., Cantley L. C. Mitogens and ion fluxes. Annu Rev Physiol. 1988;50:207–223. doi: 10.1146/annurev.ph.50.030188.001231. [DOI] [PubMed] [Google Scholar]
  29. Striker G. E., Striker L. J. Glomerular cell culture. Lab Invest. 1985 Aug;53(2):122–131. [PubMed] [Google Scholar]
  30. Tanabe T., Takeshima H., Mikami A., Flockerzi V., Takahashi H., Kangawa K., Kojima M., Matsuo H., Hirose T., Numa S. Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature. 1987 Jul 23;328(6128):313–318. doi: 10.1038/328313a0. [DOI] [PubMed] [Google Scholar]
  31. Tsuda T., Hamamori Y., Yamashita T., Fukumoto Y., Takai Y. Involvement of three intracellular messenger systems, protein kinase C, calcium ion and cyclic AMP, in the regulation of c-fos gene expression in Swiss 3T3 cells. FEBS Lett. 1986 Nov 10;208(1):39–42. doi: 10.1016/0014-5793(86)81527-7. [DOI] [PubMed] [Google Scholar]
  32. Vanhoutte P. M., Rubanyi G. M., Miller V. M., Houston D. S. Modulation of vascular smooth muscle contraction by the endothelium. Annu Rev Physiol. 1986;48:307–320. doi: 10.1146/annurev.ph.48.030186.001515. [DOI] [PubMed] [Google Scholar]
  33. Werber H. I., Emancipator S. N., Tykocinski M. L., Sedor J. R. The interleukin 1 gene is expressed by rat glomerular mesangial cells and is augmented in immune complex glomerulonephritis. J Immunol. 1987 May 15;138(10):3207–3212. [PubMed] [Google Scholar]
  34. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]

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