Antagonism of Ca2+-induced contractions of K+-depolarized smooth musle by local anaesthetics

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Abstract

Drugs known to interact with Na+ channels were compared as antagonists of Ca2+-induced contractions of K+-depolarized taenia preparations from guinea-pig caecum. Tetracaine ((apparent pA2 5.3 ± 0.2), quinidine (5.2 ± 0.1) quinine (5.1 ± 0.1), d-propranolol (4.7 ± 0.1), 1-propranolol (4.7 ± 0.1), lignocaine (4.0 ± 0.1) and procaine (3.6 ± 0.1) displaced cumulative concentration-response curves to Ca2+ to the right without depression the maximal response. The slopes of Arunlakshana and Schild plots were close to unity for quinidine, quinine, lignocaine and procaine. These drugs relaxed the established Ca2+-induced contractions rapidly and thus the effects of these drugs resembled the effects of low concentrations of verapamil. However, the effects of the local anaesthetics were increased in the presence of sodium salicylate (5–10 mM) which increases the negative surface charge. In contrast the effects of verapamil were decreased by salicylate. Veratridine (10–100 μM), which activates Na+ channels, had only depressant effects on Ca2+-induced contractions. Thus, drugs acting on Na+ channels can also interact with Ca2+ channels but there are qualitative as well as quantitative differences between the effects of these drugs and those of drugs such as verapamil. These findings indicate different mechanisms of action for the inhibition of Ca2+-induced contractions by local anaesthetics and verapamil.

References (36)

  • O. Arunlakshana et al.

    Some quantitative uses of drug antagonists

    Br. J. Pharmacol. Chemother.

    (1959)
  • W.A. Catterall

    Inhibition of voltage-sensitive sodium channels in neuroblastoma cells by antiarrhythmic drugs

    Mol. Pharmacol.

    (1981)
  • I. Cohen et al.

    Action of salicylate ions on the electrical properties of sheep cardiac purkinje fibres

    J. Physiol.

    (1979)
  • K.R. Courtney

    Structure-activity relations for frequency-dependent sodium channel block in nerve by local anaesthetics

    J. Pharmacol. Exp. Ther.

    (1980)
  • M.B. Feinstein et al.

    Effect of local anesthetics on excitation-coupling mechanisms

    Trans. N.Y. Acad. Sci.

    (1968)
  • J.B. Galpar et al.

    Inhibition of sodium channels by D600

    Mol. Pharmacol.

    (1979)
  • G. Haeusler

    Differential effects of verapamil on excitation-contraction coupling in smooth muscle and on excitation-secretion coupling in adrenergic nerve terminals

    J. Pharmacol. Exp. Ther.

    (1972)
  • J. Hescheler et al.

    Does the organic calcium channel blocker D600 act from inside or outside on the cell membrane?

    Pflügers Arch.

    (1982)
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