Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1983 Sep;80(1):163–172. doi: 10.1111/j.1476-5381.1983.tb11062.x

Mechanism of vanadate-induced contraction of airways smooth muscle of the guinea-pig.

R A Nayler, M P Sparrow
PMCID: PMC2044972  PMID: 6652367

Abstract

The characteristics of vanadate-induced contraction of airways smooth muscle are described in isolated preparations of guinea-pig central and peripheral airways. Vanadate (1-1000 microM) induced sustained contractions of trachea and lung parenchymal strips within 1 min of challenge. It was more potent (P less than 0.001) on the lung strip (EC50 = 63 microM) than on the trachea (EC50 = 123 microM). The lung strip also developed greater maximum isometric tension (P less than 0.001) than the trachea. The efficacy on the lung strip was 2 and the trachea 0.6, relative to the response to acetylcholine (efficacy = 1). Vanadate-induced contractions of the trachea were not inhibited by atropine, mepyramine, phentolamine or indomethacin, nor after mast cell depletion by compound 48/80, showing that contractions were not mediated via specific receptors or by release of endogenous mediators of tone. Inorganic phosphate specifically inhibited vanadate responses in a dose-dependent and reversible manner, suggesting a common site of action. Contractions could be elicited in depolarized muscle and after treatment with ouabain plus propranolol, showing that membrane depolarization and inhibition of the Na, K-ATPase system were not involved in the contractile action of vanadate. Pretreatment of tracheal smooth muscle with verapamil had no influence on contractions elicited by vanadate. After removal of extracellular calcium, vanadate-induced contractions declined slowly with time, indicating that influx of extracellular calcium was not giving rise to contractions elicited by vanadate. Vanadate markedly increased the rate of calcium efflux from trachealis muscle loaded with 45Ca into both Ca2+-free and normal Krebs solutions; this is compatible with vanadate mobilizing an intracellular store of Ca2+. Such a store involving sites with Ca-ATPase activity would be consistent with the action of vanadate in isolated membrane preparations. Membrane-skinned tracheal fibres contracted by micromolar Ca2+ were relaxed by vanadate in a reversible dose-related manner, indicating that the contractile action of vanadate was not related to its interaction with proteins at the cross-bridge level.

Full text

PDF
163

Selected References

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

  1. BAUER H., GOODFORD P. J., HUETER J. THE CALCIUM CONTENT AND 45-CALCIUM UPTAKE OF THE SMOOTH MUSCLE OF THE GUINEA-PIG TAENIA COLI. J Physiol. 1965 Jan;176:163–179. doi: 10.1113/jphysiol.1965.sp007542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Broekaert A., Godfraind T. The actions of ouabain on isolated arteries. Arch Int Pharmacodyn Ther. 1973 Jun;203(2):393–395. [PubMed] [Google Scholar]
  3. Cantley L. C., Jr, Cantley L. G., Josephson L. A characterization of vanadate interactions with the (Na,K)-ATPase. Mechanistic and regulatory implications. J Biol Chem. 1978 Oct 25;253(20):7361–7368. [PubMed] [Google Scholar]
  4. Cantley L. C., Jr, Josephson L., Warner R., Yanagisawa M., Lechene C., Guidotti G. Vanadate is a potent (Na,K)-ATPase inhibitor found in ATP derived from muscle. J Biol Chem. 1977 Nov 10;252(21):7421–7423. [PubMed] [Google Scholar]
  5. Cantley L. C., Jr, Resh M. D., Guidotti G. Vanadate inhibits the red cell (Na+, K+) ATPase from the cytoplasmic side. Nature. 1978 Apr 6;272(5653):552–554. doi: 10.1038/272552a0. [DOI] [PubMed] [Google Scholar]
  6. Clausen T., Andersen T. L., Stürup-Johansen M., Petkova O. The relationship between the transport of glucose and cations across cell membranes in isolated tissues. XI. The effect of vanadate on 45Ca-efflux and sugar transport in adipose tissue and skeletal muscle. Biochim Biophys Acta. 1981 Aug 20;646(2):261–267. doi: 10.1016/0005-2736(81)90332-1. [DOI] [PubMed] [Google Scholar]
  7. Dupont Y., Bennett N. Vanadate inhibition of the Ca2+-dependent conformational change of the sarcoplasmic reticulum Ca2+-ATPase. FEBS Lett. 1982 Mar 22;139(2):237–240. doi: 10.1016/0014-5793(82)80860-0. [DOI] [PubMed] [Google Scholar]
  8. Farley J. M., Miles P. R. The sources of calcium for acetylcholine-induced contractions of dog tracheal smooth muscle. J Pharmacol Exp Ther. 1978 Nov;207(2):340–346. [PubMed] [Google Scholar]
  9. Farmer J. B., Farrar D. G., Wilson J. Antagonism of tone and prostaglandin-mediated responses in a tracheal preparation by indomethacin and SC-19220. Br J Pharmacol. 1974 Dec;52(4):559–565. doi: 10.1111/j.1476-5381.1974.tb09724.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Garcia A. G., Jurkiewicz A., Jurkiewicz N. H. Contractile effect of vanadate and other vanadium compounds on the rat vas deferens. Eur J Pharmacol. 1981 Mar 5;70(1):17–23. doi: 10.1016/0014-2999(81)90427-1. [DOI] [PubMed] [Google Scholar]
  11. Hudgins P. M., Bond G. H. Alteration by vanadate of contractility in vascular and intestinal smooth muscle preparations. Pharmacology. 1981;23(3):156–164. doi: 10.1159/000137544. [DOI] [PubMed] [Google Scholar]
  12. Karaki H., Ozaki H., Urakawa N. Effects of ouabain and potassium-free solution on the contraction of isolated blood vessels. Eur J Pharmacol. 1978 Apr 15;48(4):439–443. doi: 10.1016/0014-2999(78)90172-3. [DOI] [PubMed] [Google Scholar]
  13. Karaki H., Urakawa N. Possible role of endogenous catecholamines in the contractions induced in rabbit aorta by ouabain, sodium depletion and potassium depletion. Eur J Pharmacol. 1977 May 1;43(1):65–72. doi: 10.1016/0014-2999(77)90161-3. [DOI] [PubMed] [Google Scholar]
  14. Lindquist R. N., Lynn J. L., Jr, Lienhard G. E. Possible transition-state analogs for ribonuclease. The complexes of uridine with oxovanadium(IV) ion and vanadium(V) ion. J Am Chem Soc. 1973 Dec 26;95(26):8762–8768. doi: 10.1021/ja00807a043. [DOI] [PubMed] [Google Scholar]
  15. Lulich K. M., Mitchell H. W., Sparrow M. P. The cat lung strip as an in vitro preparation of peripheral airways: a comparison of beta-adrenoceptor agonists, autacoids and anaphylactic challenge on the lung strip and trachea. Br J Pharmacol. 1976 Sep;58(1):71–79. doi: 10.1111/j.1476-5381.1976.tb07694.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Macara I. G., Kustin K., Cantley L. C., Jr Glutathione reduces cytoplasmic vanadate. Mechanism and physiological implications. Biochim Biophys Acta. 1980 Apr 17;629(1):95–106. doi: 10.1016/0304-4165(80)90268-8. [DOI] [PubMed] [Google Scholar]
  17. Mironneau J. Excitation-contraction coupling in voltage clamped uterine smooth muscle. J Physiol. 1973 Aug;233(1):127–141. doi: 10.1113/jphysiol.1973.sp010301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Musk A. W., Tees J. G. Asthma caused by occupational exposure to vanadium compounds. Med J Aust. 1982 Feb 20;1(4):183–184. doi: 10.5694/j.1326-5377.1982.tb132251.x. [DOI] [PubMed] [Google Scholar]
  19. O'Neal S. G., Rhoads D. B., Racker E. Vanadate inhibition of sarcoplasmic reticulum Ca2+-ATPase and other ATPases. Biochem Biophys Res Commun. 1979 Aug 13;89(3):845–850. doi: 10.1016/0006-291x(79)91855-2. [DOI] [PubMed] [Google Scholar]
  20. Ozaki H., Urakawa N. Effects of vanadate on mechanical responses and Na-K pump in vascular smooth muscle. Eur J Pharmacol. 1980 Dec 5;68(3):339–347. doi: 10.1016/0014-2999(80)90531-2. [DOI] [PubMed] [Google Scholar]
  21. Peterson J. W. Vanadate ion inhibits actomyosin interaction in chemically skinned vascular smooth muscle. Biochem Biophys Res Commun. 1980 Aug 29;95(4):1846–1853. doi: 10.1016/s0006-291x(80)80114-8. [DOI] [PubMed] [Google Scholar]
  22. Potter J. M., Sparrow M. P., Simmonds W. J. Increased uptake and efflux of calcium with acetylcholine stimulation in smooth muscle of toad stomach. Aust J Exp Biol Med Sci. 1970 Aug;48(4):429–443. doi: 10.1038/icb.1970.45. [DOI] [PubMed] [Google Scholar]
  23. Schneider M., Sparrow M., Rüegg J. C. Inorganic phosphate promotes relaxation of chemically skinned smooth muscle of guinea-pig Taenia coli. Experientia. 1981;37(9):980–982. doi: 10.1007/BF01971791. [DOI] [PubMed] [Google Scholar]
  24. Solaro R. J., Holroyde M. J., Herzig J. W., Peterson J. Cardiac relaxation and myofibrillar interactions with phosphate and vanadate. Eur Heart J. 1980;Suppl A:21–27. doi: 10.1093/eurheartj/1.suppl_1.21. [DOI] [PubMed] [Google Scholar]
  25. Sparrow M. P., Mrwa U., Hofmann F., Rüegg J. C. Calmodulin is essential for smooth muscle contraction. FEBS Lett. 1981 Mar 23;125(2):141–145. doi: 10.1016/0014-5793(81)80704-1. [DOI] [PubMed] [Google Scholar]
  26. Vallières J., Scarpa A., Somlyo A. P. Subcellular fractions of smooth muscle. Isolation, substrate utilization and Ca++ transport by main pulmonary artery and mesenteric vein mitochondria. Arch Biochem Biophys. 1975 Oct;170(2):659–669. doi: 10.1016/0003-9861(75)90162-9. [DOI] [PubMed] [Google Scholar]
  27. Van Breemen C., Wuytack F., Casteels R., Martinelli B., Campailla E., Ferrari G. Stimulation of 45Ca efflux from smooth muscle cells by metabolic inhibition and high K depolarization. Pflugers Arch. 1975 Sep 9;359(3):183–196. doi: 10.1007/BF00587378. [DOI] [PubMed] [Google Scholar]
  28. ZENZ C., BARTLETT J. P., THIEDE W. H. Acute vanadium pentoxide intoxication. Arch Environ Health. 1962 Dec;5:542–546. doi: 10.1080/00039896.1962.10663328. [DOI] [PubMed] [Google Scholar]

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

RESOURCES