Evidence that cyclic GMP may regulate cyclic AMP metabolism in the isolated frog ventricle

https://doi.org/10.1016/0022-2828(81)90472-7Get rights and content

Abstract

Both acetylcholine and 8-bromo cyclic GMP depress the contractile response of the isolated frog ventricle. An investigation has been made of the effects of both substances on the metabolism of endogenous 3,5 cyclic nucleotides. The levels of adenosine 3′, 5′ cyclic monophosphate (cyclic AMP) and guanosine 3′, 5′ cyclic monophosphate (cyclic GMP) were measured after superfusing preparations with varying concentrations (10−10 to 10−4m) of acetylcholine and 8-bromo cyclic GMP. The decline in contractile force was found to be accompanied by a progressive fall in intracellular cyclic AMP and a rise in cyclic GMP levels. Both the decline in contractility and the reduction in endogenous cyclic AMP are attenuated by 10−4 theophylline. The decline in isometric twitch tension was paralleled, under all conditions, by a quantitatively equivalent reduction in the ratio cyclic AMP: cyclic GMP. The possibility that endogenous cyclic GMP may accelerate the conversion of cyclic AMP to 5 AMP, by stimulating a cyclic GMP-sensitive form of cyclic AMP phosphodiesterase, is discussed.

References (47)

  • J. Singh et al.

    Inotropic responses of the frog ventricle to dibutyryl cyclic AMP and 8-Bromo cyclic, GMP and related changes in endogenous cyclic nucleotide levels

    Biochemical Pharmacology

    (1981)
  • J. Singh et al.

    Effects of isoprenaline on contractile force and intracellular cyclic 3′, 5′ nucleotide levels in the hypodynamic frog ventricle

    FEBS Letters

    (1978)
  • C.O. Bröström et al.

    Identification of a calcium-binding protein as a calcium-dependent regulator of brain adenylate cyclase

  • J.H. Brown

    Adrenergic inhibition of catecholamine-stimulable cyclic AMP accumulation in murine atria

    Journal of Cyclic Nucleotide Research

    (1979)
  • R.A.R. Chapman

    Excitation-contraction coupling in cardiac muscle

    Progress in Biophysics and Molecular Biology

    (1979)
  • W.Y. Cheung et al.

    An endogenous Ca2+-dependent activator protein of brain adenylate cyclase and cyclic nucleotide phosphodiesterase

    Advances in Cyclic Nucleotide Research

    (1978)
  • H.A. Cole et al.

    The phosphorylation of troponin I from cardiac muscle

    Biochemical Journal

    (1975)
  • P.J. England

    Studies on the phosphorylation of the inhibitory subunit of troponin during modification of contraction in perfused rat heart

    Biochemical Journal

    (1976)
  • A. Fabiato et al.

    Calcium-induced release of calcium from the sarcoplasmic reticulum of skinned cells from adult human, dog, cat, rabbit, rat and frog hearts and from foetal hearts and new born rat ventricles

    Annals of the New York Academy of Sciences

    (1978)
  • F.W. Flitney et al.

    Effects of sodium nitroprusside on frog ventricle

    Journal of Physiology

    (1980)
  • F.W. Flitney et al.

    Depressant effect of 8-bromo guanosine 3′, 5′-cyclic monophosphate on endogenous adenosine 3′, 5′-cyclic monophosphate levels in frog ventricle

    Journal of Physiology

    (1980)
  • F.W. Flitney et al.

    Exogenous uridine 5-triphosphate enhances contractility and stimulates 3′, 5′-cyclic nucleotide metabolism in the isolated frog ventricle

    Journal of Physiology

    (1979)
  • F.W. Flitney et al.

    Inotropic responses of the frog ventricle to adenosine triphosphate and related changes in endogenous cyclic nucleotides

    Journal of Physiology

    (1980)

    • Cited by (0)

    ∗

    Present address: Department of Physiology, The University, Dundee DD 1 4HN, Scotland

    View full text
    Copyright © 1981 Published by Elsevier Ltd.