Skip to main content
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
. 1989 Dec;86(23):9529–9533. doi: 10.1073/pnas.86.23.9529

Endothelin-like pulmonary vasoconstrictor peptide release by alpha-thrombin.

D G Moon 1, M J Horgan 1, T T Andersen 1, S R Krystek Jr 1, J W Fenton 2nd 1, A B Malik 1
PMCID: PMC298530  PMID: 2687882

Abstract

The endothelial cells lining the vessel wall can modulate vasomotor tone by releasing vasoactive factors, such as endothelial-derived constricting factors. We observed that alpha-thrombin, but not catalytically inactivated alpha-thrombin, mediated the release of two pulmonary vasoconstrictor peptides into the venous effluent of guinea pig lungs. These peptides elicited a slow-onset, long-lasting pulmonary vasoconstriction similar to the effect of endothelin, an endothelial-derived 21-amino acid vasoconstrictor peptide previously isolated from cells in culture. One of the isolated peptides coelutes with endothelin upon reverse-phase HPLC with an acetonitrile gradient and has a molecular weight comparable to endothelin as determined by gel-permeation HPLC. The other vasoconstrictor peptide elutes earlier than endothelin on reverse-phase HPLC and exhibits a lower molecular weight. The studies show the release of endothelin-like pulmonary vasoconstrictor peptides in the intact lung by alpha-thrombin, a central regulatory enzyme in hemostasis.

Full text

PDF
9529

Selected References

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

  1. Bidlingmeyer B. A., Cohen S. A., Tarvin T. L. Rapid analysis of amino acids using pre-column derivatization. J Chromatogr. 1984 Dec 7;336(1):93–104. doi: 10.1016/s0378-4347(00)85133-6. [DOI] [PubMed] [Google Scholar]
  2. Easley C. W. Combinations of specific color reactions useful in the peptide mapping technique. Biochim Biophys Acta. 1965 Sep 13;107(2):386–388. doi: 10.1016/0304-4165(65)90147-9. [DOI] [PubMed] [Google Scholar]
  3. Eling T., Tainer B., Ally A., Warnock R. Separation of arachidonic acid metabolites by high-pressure liquid chromatography. Methods Enzymol. 1982;86:511–517. doi: 10.1016/0076-6879(82)86221-6. [DOI] [PubMed] [Google Scholar]
  4. Fenton J. W., 2nd, Olson T. A., Zabinski M. P., Wilner G. D. Anion-binding exosite of human alpha-thrombin and fibrin(ogen) recognition. Biochemistry. 1988 Sep 6;27(18):7106–7112. doi: 10.1021/bi00418a066. [DOI] [PubMed] [Google Scholar]
  5. Firth J. D., Ratcliffe P. J., Raine A. E., Ledingham J. G. Endothelin: an important factor in acute renal failure? Lancet. 1988 Nov 19;2(8621):1179–1182. doi: 10.1016/s0140-6736(88)90243-7. [DOI] [PubMed] [Google Scholar]
  6. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  7. Hickey K. A., Rubanyi G., Paul R. J., Highsmith R. F. Characterization of a coronary vasoconstrictor produced by cultured endothelial cells. Am J Physiol. 1985 May;248(5 Pt 1):C550–C556. doi: 10.1152/ajpcell.1985.248.5.C550. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Horgan M. J., Fenton J. W., 2nd, Malik A. B. Alpha-thrombin-induced pulmonary vasoconstriction. J Appl Physiol (1985) 1987 Nov;63(5):1993–2000. doi: 10.1152/jappl.1987.63.5.1993. [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. 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. Kaiser E., Colescott R. L., Bossinger C. D., Cook P. I. Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides. Anal Biochem. 1970 Apr;34(2):595–598. doi: 10.1016/0003-2697(70)90146-6. [DOI] [PubMed] [Google Scholar]
  13. Kimura S., Kasuya Y., Sawamura T., Shinmi O., Sugita Y., Yanagisawa M., Goto K., Masaki T. Structure-activity relationships of endothelin: importance of the C-terminal moiety. Biochem Biophys Res Commun. 1988 Nov 15;156(3):1182–1186. doi: 10.1016/s0006-291x(88)80757-5. [DOI] [PubMed] [Google Scholar]
  14. Moncada S., Gryglewski R., Bunting S., Vane J. R. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature. 1976 Oct 21;263(5579):663–665. doi: 10.1038/263663a0. [DOI] [PubMed] [Google Scholar]
  15. Rakugi H., Nakamaru M., Saito H., Higaki J., Ogihara T. Endothelin inhibits renin release from isolated rat glomeruli. Biochem Biophys Res Commun. 1988 Sep 30;155(3):1244–1247. doi: 10.1016/s0006-291x(88)81273-7. [DOI] [PubMed] [Google Scholar]
  16. Spinella M. J., Krystek S. R., Jr, Peapus D. H., Wallace B. A., Bruner C., Andersen T. T. A proposed structural model of endothelin. Pept Res. 1989 Jul-Aug;2(4):286–291. [PubMed] [Google Scholar]
  17. Tomobe Y., Miyauchi T., Saito A., Yanagisawa M., Kimura S., Goto K., Masaki T. Effects of endothelin on the renal artery from spontaneously hypertensive and Wistar Kyoto rats. Eur J Pharmacol. 1988 Aug 2;152(3):373–374. doi: 10.1016/0014-2999(88)90736-4. [DOI] [PubMed] [Google Scholar]
  18. Whittle B. J., Esplugues J. V. Induction of rat gastric damage by the endothelium-derived peptide, endothelin. Br J Pharmacol. 1988 Dec;95(4):1011–1013. doi: 10.1111/j.1476-5381.1988.tb11733.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. 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 Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES