Skip to main content
Log in

Effects of endothelin-1 on the isolated guinea-pig ileum: role of Na+ ions

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

Endothelin-1 induced an unusual transient biphasic effect (relaxation followed by contraction) in the isolated guinea-pig ileum. The contractile component of the response was concentration-dependent in the dose range studied, but the relaxant component was not. Neuronal mechanisms and cyclic GMP do not seem to be involved in the relaxing effect since this component was not affected by either tetrodotoxin, atropine or methylene blue. Endothelin-1 induced desensitization which was well characterized for the contractile component of the response, and was only partially reversed after a 3-h resting period. The effects of endothelin-1 were particularly sensitive to decreases in the Na+ gradient induced either by lowering the Na+ concentration in the medium or by treating the tissue with ouabain or by a previous treatment with acetylcholine. Amiloride partially inhibited the response induced by endothelin-1 indicating that Na+ channels and/or Na+/H+ exchange are probably involved in its action. Our results suggest that the contractile response induced by endothelin-1 in the isolated guinea-pig ileum depends greatly on Na+ ions, in contrast to the responses observed in vascular smooth muscle.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aaronson P, van Breemen C (1981) Effects of sodium gradient manipulation upon cellular calcium, Ca fluxes and cellular sodium in the guinea-pig taenia coli. J Physiol 319:443–461

    CAS  PubMed  Google Scholar 

  • Aboulafla J, Capocci H, Paiva ACM, Paiva TB (1987) Sodium-dependence of the non-specific desensitization of the guinea-pig ileum induced by acetylcholine and histamine. Br J Pharmac 90:347–353

    Google Scholar 

  • Bolton TB (1979) Mechanisms of actions of transmitters and other substances on smooth muscle. Physiol Rev 59:606–718

    CAS  PubMed  Google Scholar 

  • Borges R, von Grafenstein H, Knight DE (1989a) Tissue selectivity of endothelin. Eur J Pharmac 165:223–230

    CAS  Google Scholar 

  • Borges R, Carter DV, von Grafenstein H, Halliday J, Knight DE (1989b) Ionic requirements of the endothelin response in aorta and portal vein. Circ Res 65:265–271

    CAS  PubMed  Google Scholar 

  • Catterall WA (1986) Molecular properties of voltage-sensitive sodium channels. Ann Rev Biochem 55:953–985

    CAS  PubMed  Google Scholar 

  • Criscione L, Thomann H, Rodriguez C, Egleme C, Chiesi M (1989) Blockade of endothelin-induced contractions by dichlorobenzamil: mechanism of action. Biochem Biophys Res Commun 163:247–254

    Article  CAS  PubMed  Google Scholar 

  • de Nucci G, Thomas R, D'Orleans-Just, Antunes E, Walder C, Warner TD, Vane JR (1988) Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci USA 85:9797–9800

    PubMed  Google Scholar 

  • Eglen RM, Michel AD, Sharif NA, Swank SR, Whiting RL (1989) The pharmacological properties of the peptide, endothelin. Br J Pharmacol 97:1297–1307

    CAS  PubMed  Google Scholar 

  • Hiley CR, Pelton JT, Miller RC (1989) Effects of endothelin on field stimulated rat vas deferens and guinea-pig ileum. Br J Pharmacol 96 :104P

  • James-Kracke MR, Roufogalis BD (1981) Alteration of smooth muscle contractility after muscarinic agonist-induced K+ loss. Br J Pharmacol 72:609–619

    CAS  PubMed  Google Scholar 

  • Joiner PD (1973) Studies on the loss of acetylcholine sensitivity in ileal muscle. J Pharmacol Exp Ther 186:552–561

    CAS  PubMed  Google Scholar 

  • Kishimoto T, Urakawa N (1982) Effects of ouabain on high-K induced contractions of various smooth muscle tissues in the guinea-pig. Jpn J Pharmacol 32:551–561

    CAS  PubMed  Google Scholar 

  • Kloog Y, Ambar I, Sokolovsky M, Kochva E, Wollberg Z, Bdolah A (1988) Sarafotoxin, a novel vasoconstrictor peptide: phosphoinositide hydrolysis in rat heart and brain. Science 242:268–270

    CAS  PubMed  Google Scholar 

  • Kozuka M, Ito T, Hirose S, Takahashi K, Hagiwara H (1989) Endothelin induces two types of contractions of rat uterus: phasic contractions by way of voltage-dependent calcium channels and developing contractions through a second type of calcium channels. Biochem Biophys Res Commun 159:317–323

    Article  CAS  PubMed  Google Scholar 

  • Kuriyama H, Ito Y, Suzuki H, Kitamura K, Itoh T (1982) Factors modifying contraction-relaxation cycle in vascular smooth muscles. Am J Physiol 243:H641-H660

    CAS  PubMed  Google Scholar 

  • Maggi CA, Giuliani S, Patacchini R, Rovero P, Giachetti A, Meli A (1989) The activity of peptides of the endothelin family in various mammalian smooth muscle preparations. Eur J Pharmacol 174:23–31

    Article  CAS  PubMed  Google Scholar 

  • Meyer-Lehnert H, Warming C, Predel H-G, Backer A, Stelkens H, Kramer HJ (1989) Effects of endothelin on sodium transport mechanisms: potential role in cellular Ca2+ mobilization. Biochem Biophys Res Commun 163:458–465

    CAS  PubMed  Google Scholar 

  • Miasiro N, Paiva ACM (1990) Homologous desensitization of the effects of endothelin on rabbit aorta rings and on cultured rat aorta smooth muscle cells. Eur J Pharmacol 179:151–158

    Article  CAS  PubMed  Google Scholar 

  • Nouailhetas VLA, Shimuta SI, Paiva ACM, Paiva TB (1985) Calcium and sodium dependence of the biphasic response of the guinea-pig ileum to agonists. Eur J Pharmacol 116:41–47

    Article  CAS  PubMed  Google Scholar 

  • Paiva TB, Goissis G, Juliano L, Miyamoto ME, Paiva ACM (1974) Angiotensin-like and antagonistic activities of N-terminal modified [8-leucine] angiotensin II peptides. J Med Chem 17:238–241

    Article  CAS  Google Scholar 

  • Paiva TB, Aboulafia J, Nouailhetas VLA, Paiva ACM (1976a) Tachyphylaxis and angiotensin receptors. Gen Pharmacol 7:185–188

    CAS  PubMed  Google Scholar 

  • Paiva TB, Mendes GB, Aboulafia J, Paiva ACM (1976b) Evidence against cholinergic mediation of the effect of angiotensin II on the guinea-pig ileum. Pflügers Arch 365:129–133

    Article  CAS  PubMed  Google Scholar 

  • Paiva TB, Paiva ACM, Shimuta SI (1988) Role of sodium ions in angiotensin II tachyphylaxis in the guinea-pig ileum and taenia coli. Naunyn-Schmiedeberg's Arch Pharmacol 337:656–660

    Article  CAS  Google Scholar 

  • Paton WDM, Rothschild AM (1965) The changes in response and in ionic content of smooth muscle produced by acetylcholine action and by calcium deficiency. Br J Pharmacol 24:437–448

    CAS  Google Scholar 

  • Saida K, Mitsui Y, Ishida N (1989) A novel peptide, vasoactive intestinal contractor, of a new (endothelin) peptide family. J Biol Chem 264:14613–14616

    CAS  PubMed  Google Scholar 

  • Sakata K, Ozaki H, Kwon S-C, Karaki H (1989) Effects of endothelin on the mechanical activity and cytosolic calcium levels of various types of smooth muscle. Br J Pharmacol 98:483–492

    CAS  PubMed  Google Scholar 

  • Shimuta SI, Nouailhetas VLA, Valero VB, Paiva ACM, Paiva TB (1982) Effect of sodium concentration and of atropine on the contractile response of the guinea-pig ileum to potassium ions. Pflügers Arch 394:186–190

    Article  CAS  PubMed  Google Scholar 

  • Shimuta SI, Nouailhetas VLA, Paiva TB, Paiva ACM (1987) Amiloride inhibition of guinea-pig contractile responses to acetylcholine. Brazilian J Med Biol Res 20:251–259

    CAS  Google Scholar 

  • Simpson AWM, Ashley CC (1989) Endothelin evoked Ca2+ transients and oscillations in A10 vascular smooth muscle cells. Biochem Biophys Res Commun 163:1223–1229

    Article  CAS  PubMed  Google Scholar 

  • Tanabe T, Takeshima H, Mikami A, Flockerzi V, Takahashi H, Kangawa K, Kojima M, Matsuo H, Hirose T, Numa S (1987) Primary structures of the receptor for calcium channel blockers from skeletal muscle. Nature 328:313–318

    Article  CAS  PubMed  Google Scholar 

  • Uchida Y, Ninomiya H, Saotome M, Nomura A, Ohtsuka M, Yanagisawa M, Goto K, Masaki T, Hasegawa S (1988) Endothelin, a novel vasoconstrictor peptide, as potent bronchoconstrictor. Eur J Pharmacol 154:227–228

    Article  CAS  PubMed  Google Scholar 

  • Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415

    Article  CAS  PubMed  Google Scholar 

  • Yanagisawa M, Masaki T (1989) Molecular biology and biochemistry of the endothelins. Trends Pharmacol Sci 10:374–378

    CAS  PubMed  Google Scholar 

  • Wiklund NP, Ohlen A, Wiklund CU, Cederqvist B, Hedgvist P, Gustafsson LE (1989) Neuromuscular actions of endothelin on smooth, cardiac and skeletal muscle from guinea-pig, rat and rabbit. Acta Physiol Scand 137:399–407

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Send offprint requests to N. Miasiro at the above address

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miasiro, N., Paiva, A.C.M. Effects of endothelin-1 on the isolated guinea-pig ileum: role of Na+ ions. Naunyn-Schmiedeberg's Arch Pharmacol 342, 706–712 (1990). https://doi.org/10.1007/BF00175716

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00175716

Key words

Navigation