Premium
Mechanism of vanadate‐induced contraction of airways smooth muscle of the guinea‐pig
Author(s) -
Nayler Ross A.,
Sparrow Malcolm P.
Publication year - 1983
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1983.tb11062.x
Subject(s) - vanadate , trachealis muscle , verapamil , ouabain , calcium , endocrinology , contraction (grammar) , phentolamine , medicine , extracellular , muscle contraction , chemistry , biophysics , biology , propranolol , biochemistry , sodium , organic chemistry , charybdotoxin
1 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 μ M ) induced sustained contractions of trachea and lung parenchymal strips within 1 min of challenge. It was more potent ( P < 0.001) on the lung strip (EC 50 = 63 μ M ) than on the trachea (EC 50 =123 μ M ). The lung strip also developed greater maximum isometric tension ( P < 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). 2 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. 3 Inorganic phosphate specifically inhibited vanadate responses in a dose‐dependent and reversible manner, suggesting a common site of action. 4 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. 5 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. 6 Vanadate markedly increased the rate of calcium efflux from trachealis muscle loaded with 45 Ca into both Ca 2+ ‐free and normal Krebs solutions; this is compatible with vanadate mobilizing an intracellular store of Ca 2+ . Such a store involving sites with Ca‐ATPase activity would be consistent with the action of vanadate in isolated membrane preparations. 7 Membrane‐skinned tracheal fibres contracted by micromolar Ca 2+ 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.