Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Feb;114(3):720–726. doi: 10.1111/j.1476-5381.1995.tb17198.x

Different pressor and bronchoconstrictor properties of human big-endothelin-1, 2 (1-38) and 3 in ketamine/xylazine-anaesthetized guinea-pigs.

J P Gratton 1, G A Rae 1, A Claing 1, S Télémaque 1, P D'Orléans-Juste 1
PMCID: PMC1510030  PMID: 7735698

Abstract

1. In the present study, the precursors of endothelin-1, endothelin-2 and endothelin-3 were tested for their pressor and bronchoconstrictor properties in the anaesthetized guinea-pig. In addition, the effects of big-endothelin-1 and endothelin-1 were assessed under urethane or ketamine/xylazine anaesthesia. 2. When compared to ketamine/xylazine, urethane markedly depressed the pressor and bronchoconstrictor properties of endothelin-1 and big-endothelin-1. 3. Under ketamine/xylazine anaesthesia, the three endothelins induced a biphasic increase of mean arterial blood pressure. In contrast, big-endothelin-1, as well as big-endothelin-2 (1-38), induced only sustained increase in blood pressure whereas big-endothelin-3 was inactive at doses up to 25 nmol kg-1. 4. Big-endothelin-1, but not big-endothelin-2, induced a significant increase in airway resistance. Yet, endothelin-1, endothelin-2 and endothelin-3 were equipotent as bronchoconstrictor agents. 5. Big-endothelin-1, endothelin-1 and endothelin-2, but not big-endothelin-2, triggered a marked release of prostacyclin and thromboxane A2 from the guinea-pig perfused lung. 6. Our results suggest the presence of a phosphoramidon-sensitive endothelin-converting enzyme (ECE) which is responsible for the conversion of big-endothelin-1 and big-endothelin-2 to their active moieties, endothelin-1 and 2. However, the lack of bronchoconstrictor and eicosanoid-releasing properties of big-endothelin-2, as opposed to endothelin-2 or big-endothelin-1, suggests the presence of two distinct phosphoramidon-sensitive ECEs in the guinea-pig.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
720

Selected References

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

  1. Arinami T., Ishikawa M., Inoue A., Yanagisawa M., Masaki T., Yoshida M. C., Hamaguchi H. Chromosomal assignments of the human endothelin family genes: the endothelin-1 gene (EDN1) to 6p23-p24, the endothelin-2 gene (EDN2) to 1p34, and the endothelin-3 gene (EDN3) to 20q13.2-q13.3. Am J Hum Genet. 1991 May;48(5):990–996. [PMC free article] [PubMed] [Google Scholar]
  2. Bloch K. D., Eddy R. L., Shows T. B., Quertermous T. cDNA cloning and chromosomal assignment of the gene encoding endothelin 3. J Biol Chem. 1989 Oct 25;264(30):18156–18161. [PubMed] [Google Scholar]
  3. Couture R., Kérouac R. Plasma protein extravasation induced by mammalian tachykinins in rat skin: influence of anaesthetic agents and an acetylcholine antagonist. Br J Pharmacol. 1987 Jun;91(2):265–273. doi: 10.1111/j.1476-5381.1987.tb10281.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. D'Orléans-Juste P., Lidbury P. S., Telemaque S., Warner T. D., Vane J. R. Human big endothelin releases prostacyclin in vivo and in vitro through a phosphoramidon-sensitive conversion to endothelin-1. J Cardiovasc Pharmacol. 1991;17 (Suppl 7):S251–S255. doi: 10.1097/00005344-199100177-00072. [DOI] [PubMed] [Google Scholar]
  5. D'Orléans-Juste P., Télémaque S., Claing A. Different pharmacological profiles of big-endothelin-3 and big-endothelin-1 in vivo and in vitro. Br J Pharmacol. 1991 Oct;104(2):440–444. doi: 10.1111/j.1476-5381.1991.tb12448.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fukuroda T., Noguchi K., Tsuchida S., Nishikibe M., Ikemoto F., Okada K., Yano M. Inhibition of biological actions of big endothelin-1 by phosphoramidon. Biochem Biophys Res Commun. 1990 Oct 30;172(2):390–395. doi: 10.1016/0006-291x(90)90685-g. [DOI] [PubMed] [Google Scholar]
  7. Gardiner S. M., Kemp P. A., Bennett T. Inhibition by phosphoramidon of the regional haemodynamic effects of proendothelin-2 and -3 in conscious rats. Br J Pharmacol. 1992 Oct;107(2):584–590. doi: 10.1111/j.1476-5381.1992.tb12787.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Howard P. G., Plumpton C., Davenport A. P. Anatomical localization and pharmacological activity of mature endothelins and their precursors in human vascular tissue. J Hypertens. 1992 Nov;10(11):1379–1386. doi: 10.1097/00004872-199211000-00010. [DOI] [PubMed] [Google Scholar]
  9. Ishikawa K., Ihara M., Noguchi K., Mase T., Mino N., Saeki T., Fukuroda T., Fukami T., Ozaki S., Nagase T. Biochemical and pharmacological profile of a potent and selective endothelin B-receptor antagonist, BQ-788. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4892–4896. doi: 10.1073/pnas.91.11.4892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kashiwabara T., Inagaki Y., Ohta H., Iwamatsu A., Nomizu M., Morita A., Nishikori K. Putative precursors of endothelin have less vasoconstrictor activity in vitro but a potent pressor effect in vivo. FEBS Lett. 1989 Apr 10;247(1):73–76. doi: 10.1016/0014-5793(89)81243-8. [DOI] [PubMed] [Google Scholar]
  11. Matsumura Y., Fujita K., Takaoka M., Morimoto S. Big endothelin-3-induced hypertension and its inhibition by phosphoramidon in anaesthetized rats. Eur J Pharmacol. 1993 Jan 5;230(1):89–93. doi: 10.1016/0014-2999(93)90414-d. [DOI] [PubMed] [Google Scholar]
  12. Mattera G. G., Eglezos A., Renzetti A. R., Mizrahi J. Comparison of the cardiovascular and neural activity of endothelin-1, -2, -3 and respective proendothelins: effects of phosphoramidon and thiorphan. Br J Pharmacol. 1993 Sep;110(1):331–337. doi: 10.1111/j.1476-5381.1993.tb13813.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nedergaard O. A. Cocaine-like effect of ketamine on vascular adrenergic neurones. Eur J Pharmacol. 1973 Aug;23(2):153–161. doi: 10.1016/0014-2999(73)90051-4. [DOI] [PubMed] [Google Scholar]
  14. Noguchi K., Noguchi Y., Hirose H., Nishikibe M., Ihara M., Ishikawa K., Yano M. Role of endothelin ETB receptors in bronchoconstrictor and vasoconstrictor responses in guinea-pigs. Eur J Pharmacol. 1993 Mar 16;233(1):47–51. doi: 10.1016/0014-2999(93)90347-k. [DOI] [PubMed] [Google Scholar]
  15. Payne A. N., Whittle B. J. Potent cyclo-oxygenase-mediated bronchoconstrictor effects of endothelin in the guinea-pig in vivo. Eur J Pharmacol. 1988 Dec 13;158(3):303–304. doi: 10.1016/0014-2999(88)90085-4. [DOI] [PubMed] [Google Scholar]
  16. Pollock D. M., Divish B. J., Milicic I., Novosad E. I., Burres N. S., Opgenorth T. J. In vivo characterization of a phosphoramidon-sensitive endothelin-converting enzyme in the rat. Eur J Pharmacol. 1993 Feb 16;231(3):459–464. doi: 10.1016/0014-2999(93)90124-z. [DOI] [PubMed] [Google Scholar]
  17. Pons F., Boichot E., Lagente V., Touvay C., Mencia-Huerta J. M., Braquet P. Role of endothelin in pulmonary function. Pulm Pharmacol. 1992 Sep;5(3):213–219. doi: 10.1016/0952-0600(92)90043-g. [DOI] [PubMed] [Google Scholar]
  18. Pons F., Loquet I., Touvay C., Roubert P., Chabrier P. E., Mencia-Huerta J. M., Braquet P. Comparison of the bronchopulmonary and pressor activities of endothelin isoforms ET-1, ET-2, and ET-3 and characterization of their binding sites in guinea pig lung. Am Rev Respir Dis. 1991 Feb;143(2):294–300. doi: 10.1164/ajrccm/143.2.294. [DOI] [PubMed] [Google Scholar]
  19. Pons F., Touvay C., Lagente V., Mencia-Huerta J. M., Braquet P. Bronchopulmonary and pressor activities of endothelin-1 (ET-1), ET-2, ET-3, and big ET-1 in the guinea pig. J Cardiovasc Pharmacol. 1991;17 (Suppl 7):S326–S328. doi: 10.1097/00005344-199100177-00093. [DOI] [PubMed] [Google Scholar]
  20. Sawamura T., Shinmi O., Kishi N., Sugita Y., Yanagisawa M., Goto K., Masaki T., Kimura S. Characterization of phosphoramidon-sensitive metalloproteinases with endothelin-converting enzyme activity in porcine lung membrane. Biochim Biophys Acta. 1993 Feb 13;1161(2-3):295–302. doi: 10.1016/0167-4838(93)90228-j. [DOI] [PubMed] [Google Scholar]
  21. Shimada K., Takahashi M., Tanzawa K. Cloning and functional expression of endothelin-converting enzyme from rat endothelial cells. J Biol Chem. 1994 Jul 15;269(28):18275–18278. [PubMed] [Google Scholar]
  22. Traber D. L., Wilson R. D. Involvement of the sympathetic nervous system in the pressor response to ketamine. Anesth Analg. 1969 Mar-Apr;48(2):248–252. [PubMed] [Google Scholar]
  23. Wang Y. X., Pang C. C. Halothane inhibits the pressor effect of diphenyleneiodonium. Br J Pharmacol. 1993 Aug;109(4):1186–1191. doi: 10.1111/j.1476-5381.1993.tb13747.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yorimitsu K., Shinmi O., Nishiyama M., Moroi K., Sugita Y., Saito T., Inagaki Y., Masaki T., Kimura S. Effect of phosphoramidon on big endothelin-2 conversion into endothelin-2 in human renal adenocarcinoma (ACHN) cells. Analysis of endothelin-2 biosynthetic pathway. FEBS Lett. 1992 Dec 21;314(3):395–398. doi: 10.1016/0014-5793(92)81513-l. [DOI] [PubMed] [Google Scholar]

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

RESOURCES