Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1990 Mar 1;266(2):415–420. doi: 10.1042/bj2660415

Endothelin stimulates phosphatidylinositol hydrolysis and DNA synthesis in brain capillary endothelial cells.

P Vigne 1, R Marsault 1, J P Breittmayer 1, C Frelin 1
PMCID: PMC1131147  PMID: 2156495

Abstract

Endothelin-1 (ET-1) is a novel vasoconstricting and cardiotonic peptide that is synthesized by the vascular endothelium. Bovine aortic endothelial cells which secrete ET in vitro lack membrane receptor sites for the peptide. Endothelial cells from rat brain microvessels that do not secrete ET in vitro express large amounts of high-affinity receptors for 125I-labelled ET-1 (Kd 0.8 nM). The ET receptor is recognized by sarafotoxin S6b and the different ET peptides with the following order of potency: ET-1 (Kd 0.5 nM) approximately equal to ET-2 (Kd 0.7 nM) greater than sarafotoxin S6b (Kd 27 nM) greater than ET-3 (Kd 450 nM). This structure-activity relationship is different from those found in vascular smooth muscle cells, renal cells and cardiac cells. ET-1 stimulates DNA synthesis in brain capillary endothelial cells. It is more potent than basic fibroblast growth factor. The action of ET on endothelial cells from microvessels involves phosphatidylinositol hydrolysis and intracellular Ca2+ mobilization. These observations suggest that brain endothelial cells might be an important target for ET.

Full text

PDF
415

Selected References

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

  1. Ambar I., Kloog Y., Schvartz I., Hazum E., Sokolovsky M. Competitive interaction between endothelin and sarafotoxin: Binding and phosphoinositides hydrolysis in rat atria and brain. Biochem Biophys Res Commun. 1989 Jan 16;158(1):195–201. doi: 10.1016/s0006-291x(89)80197-4. [DOI] [PubMed] [Google Scholar]
  2. Badr K. F., Munger K. A., Sugiura M., Snajdar R. M., Schwartzberg M., Inagami T. High and low affinity binding sites for endothelin on cultured rat glomerular mesangial cells. Biochem Biophys Res Commun. 1989 Jun 15;161(2):776–781. doi: 10.1016/0006-291x(89)92667-3. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  5. Dashwood M., Turner M., Jacobs M. Endothelin-1: contractile responses and autoradiographic localization of receptors in rabbit blood vessels. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S183–S185. [PubMed] [Google Scholar]
  6. Emori T., Hirata Y., Ohta K., Shichiri M., Marumo F. Secretory mechanism of immunoreactive endothelin in cultured bovine endothelial cells. Biochem Biophys Res Commun. 1989 Apr 14;160(1):93–100. doi: 10.1016/0006-291x(89)91625-2. [DOI] [PubMed] [Google Scholar]
  7. Gospodarowicz D., Neufeld G., Schweigerer L. Fibroblast growth factor: structural and biological properties. J Cell Physiol Suppl. 1987;Suppl 5:15–26. doi: 10.1002/jcp.1041330405. [DOI] [PubMed] [Google Scholar]
  8. Griendling K. K., Tsuda T., Alexander R. W. Endothelin stimulates diacylglycerol accumulation and activates protein kinase C in cultured vascular smooth muscle cells. J Biol Chem. 1989 May 15;264(14):8237–8240. [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. Inoue A., Yanagisawa M., Kimura S., Kasuya Y., Miyauchi T., Goto K., Masaki T. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2863–2867. doi: 10.1073/pnas.86.8.2863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ishikawa T., Yanagisawa M., Kimura S., Goto K., Masaki T. Positive inotropic action of novel vasoconstrictor peptide endothelin on guinea pig atria. Am J Physiol. 1988 Oct;255(4 Pt 2):H970–H973. doi: 10.1152/ajpheart.1988.255.4.H970. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Kloog Y., Ambar I., Sokolovsky M., Kochva E., Wollberg Z., Bdolah A. Sarafotoxin, a novel vasoconstrictor peptide: phosphoinositide hydrolysis in rat heart and brain. Science. 1988 Oct 14;242(4876):268–270. doi: 10.1126/science.2845579. [DOI] [PubMed] [Google Scholar]
  14. Komuro I., Kurihara H., Sugiyama T., Yoshizumi M., Takaku F., Yazaki Y. Endothelin stimulates c-fos and c-myc expression and proliferation of vascular smooth muscle cells. FEBS Lett. 1988 Oct 10;238(2):249–252. doi: 10.1016/0014-5793(88)80489-7. [DOI] [PubMed] [Google Scholar]
  15. Kumagaye S., Kuroda H., Nakajima K., Watanabe T. X., Kimura T., Masaki T., Sakakibara S. Synthesis and disulfide structure determination of porcine endothelin: an endothelium-derived vasoconstricting peptide. Int J Pept Protein Res. 1988 Dec;32(6):519–526. doi: 10.1111/j.1399-3011.1988.tb01383.x. [DOI] [PubMed] [Google Scholar]
  16. Lambert T. L., Kent R. S., Whorton A. R. Bradykinin stimulation of inositol polyphosphate production in porcine aortic endothelial cells. J Biol Chem. 1986 Nov 15;261(32):15288–15293. [PubMed] [Google Scholar]
  17. Marsden P. A., Danthuluri N. R., Brenner B. M., Ballermann B. J., Brock T. A. Endothelin action on vascular smooth muscle involves inositol trisphosphate and calcium mobilization. Biochem Biophys Res Commun. 1989 Jan 16;158(1):86–93. doi: 10.1016/s0006-291x(89)80180-9. [DOI] [PubMed] [Google Scholar]
  18. Martin E. R., Marsden P. A., Brenner B. M., Ballermann B. J. Identification and characterization of endothelin binding sites in rat renal papillary and glomerular membranes. Biochem Biophys Res Commun. 1989 Jul 14;162(1):130–137. doi: 10.1016/0006-291x(89)91972-4. [DOI] [PubMed] [Google Scholar]
  19. Muldoon L. L., Rodland K. D., Forsythe M. L., Magun B. E. Stimulation of phosphatidylinositol hydrolysis, diacylglycerol release, and gene expression in response to endothelin, a potent new agonist for fibroblasts and smooth muscle cells. J Biol Chem. 1989 May 25;264(15):8529–8536. [PubMed] [Google Scholar]
  20. Nakaki T., Nakayama M., Yamamoto S., Kato R. Endothelin-mediated stimulation of DNA synthesis in vascular smooth muscle cells. Biochem Biophys Res Commun. 1989 Feb 15;158(3):880–883. doi: 10.1016/0006-291x(89)92804-0. [DOI] [PubMed] [Google Scholar]
  21. Naruse M., Naruse K., Kurimoto F., Horiuchi J., Tsuchiya K., Kawana M., Kato Y., Zeng Z. P., Sakurai H., Demura H. Radioimmunoassay for endothelin and immunoreactive endothelin in culture medium of bovine endothelial cells. Biochem Biophys Res Commun. 1989 Apr 28;160(2):662–668. doi: 10.1016/0006-291x(89)92484-4. [DOI] [PubMed] [Google Scholar]
  22. Pirotton S., Raspe E., Demolle D., Erneux C., Boeynaems J. M. Involvement of inositol 1,4,5-trisphosphate and calcium in the action of adenine nucleotides on aortic endothelial cells. J Biol Chem. 1987 Dec 25;262(36):17461–17466. [PubMed] [Google Scholar]
  23. Simonson M. S., Wann S., Mené P., Dubyak G. R., Kester M., Nakazato Y., Sedor J. R., Dunn M. J. Endothelin stimulates phospholipase C, Na+/H+ exchange, c-fos expression, and mitogenesis in rat mesangial cells. J Clin Invest. 1989 Feb;83(2):708–712. doi: 10.1172/JCI113935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Takuwa N., Takuwa Y., Yanagisawa M., Yamashita K., Masaki T. A novel vasoactive peptide endothelin stimulates mitogenesis through inositol lipid turnover in Swiss 3T3 fibroblasts. J Biol Chem. 1989 May 15;264(14):7856–7861. [PubMed] [Google Scholar]
  25. Van Renterghem C., Vigne P., Barhanin J., Schmid-Alliana A., Frelin C., Lazdunski M. Molecular mechanism of action of the vasoconstrictor peptide endothelin. Biochem Biophys Res Commun. 1988 Dec 30;157(3):977–985. doi: 10.1016/s0006-291x(88)80970-7. [DOI] [PubMed] [Google Scholar]
  26. Vigne P., Breittmayer J. P., Duval D., Frelin C., Lazdunski M. The Na+/Ca2+ antiporter in aortic smooth muscle cells. Characterization and demonstration of an activation by phorbol esters. J Biol Chem. 1988 Jun 15;263(17):8078–8083. [PubMed] [Google Scholar]
  27. Vigne P., Champigny G., Marsault R., Barbry P., Frelin C., Lazdunski M. A new type of amiloride-sensitive cationic channel in endothelial cells of brain microvessels. J Biol Chem. 1989 May 5;264(13):7663–7668. [PubMed] [Google Scholar]
  28. Vigne P., Lazdunski M., Frelin C. The inotropic effect of endothelin-1 on rat atria involves hydrolysis of phosphatidylinositol. FEBS Lett. 1989 Jun 5;249(2):143–146. doi: 10.1016/0014-5793(89)80611-8. [DOI] [PubMed] [Google Scholar]
  29. Warner T. D., de Nucci G., Vane J. R. Rat endothelin is a vasodilator in the isolated perfused mesentery of the rat. Eur J Pharmacol. 1989 Jan 17;159(3):325–326. doi: 10.1016/0014-2999(89)90167-2. [DOI] [PubMed] [Google Scholar]
  30. Watanabe H., Miyazaki H., Kondoh M., Masuda Y., Kimura S., Yanagisawa M., Masaki T., Murakami K. Two distinct types of endothelin receptors are present on chick cardiac membranes. Biochem Biophys Res Commun. 1989 Jun 30;161(3):1252–1259. doi: 10.1016/0006-291x(89)91377-6. [DOI] [PubMed] [Google Scholar]
  31. Wollberg Z., Bdolah A., Kochva E. Vasoconstrictor effects of sarafotoxins in rabbit aorta: structure-function relationships. Biochem Biophys Res Commun. 1989 Jul 14;162(1):371–376. doi: 10.1016/0006-291x(89)92006-8. [DOI] [PubMed] [Google Scholar]
  32. Wollberg Z., Shabo-Shina R., Intrator N., Bdolah A., Kochva E., Shavit G., Oron Y., Vidne B. A., Gitter S. A novel cardiotoxic polypeptide from the venom of Atractaspis engaddensis (burrowing asp): cardiac effects in mice and isolated rat and human heart preparations. Toxicon. 1988;26(6):525–534. doi: 10.1016/0041-0101(88)90232-2. [DOI] [PubMed] [Google Scholar]
  33. Yanagisawa M., Inoue A., Ishikawa T., Kasuya Y., Kimura S., Kumagaye S., Nakajima K., Watanabe T. X., Sakakibara S., Goto K. Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6964–6967. doi: 10.1073/pnas.85.18.6964. [DOI] [PMC free article] [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]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES