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Adenine nucleotide regulation of particulate guanylate cyclase from rat lung

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Abstract

Adenine nucleotides activate basal particulate guanylate cyclase in rat lung membranes. Activation is specific for adenine and not guanine, cytidine or uridine nucleotides. The concentration of adenine nucleotides yielding half-maximum activation of particulate guanylate cyclase is 0.1 mM and this nucleotide activates the enzyme by increasing maximum velocity 11-fold without altering affinity for substrate. Activation is specific for particulate guanylate cyclase, since soluble enzyme is inhibited by adenine nucleotides. Similarly, activation is specific for magnesium as the enzyme substrate cation cofactor, since adenine nucleotides inhibit particulate guanylate cyclase when manganese is used. Adenine nucleotide regulation of particulate guanylate cyclase may occur by a different molecular mechanism compared to other activators, since the effects of these nucleotides are synergistic with those of detergent, hemin and atrial natriuretic peptides. Cystamine inhibits adenine nucleotide activation of particulate guanylate cyclase at concentrations having minimal effects on basal enzyme activity suggesting a role for critical sulfhydryls in mechanisms underlying nucleotide regulation of particulate guanylate cyclase. Purification and quantitative recovery of particulate guanylate cyclase by substrate affinity chromatography results in the loss of adenine nucleotide regulation. These data suggest that adenine nucleotides may be important in the regulation of basal and activated particulate guanylate cyclase and may be mediated by an adenine nucleotide-binding protein which is separate from that enzyme.

References (30)

  • S.A. Waldman et al.

    J. Biol. Chem.

    (1984)
  • H. Kurose et al.

    FEBS Lett.

    (1987)
  • A. Steiner et al.

    J. Biol. Chem.

    (1972)
  • H. Kimura et al.

    J. Biol. Chem.

    (1975)
  • S.A. Waldman et al.

    J. Biol. Chem.

    (1984)
  • J.G. Hardman et al.

    J. Biol. Chem.

    (1969)
  • E. Ishikawa et al.

    J. Biol. Chem.

    (1969)
  • H.J. Brandwein et al.

    J. Biol. Chem.

    (1982)
  • H.J. Brandwein et al.

    J. Biol. Chem.

    (1981)
  • D.L. Song et al.

    FEBS Lett.

    (1988)
  • T. Kuno et al.

    J. Biol. Chem.

    (1986)
  • R. Takayanagi et al.

    Biochem. Biophys. Res. Commun.

    (1987)
  • R. Takayanagi et al.

    J. Biol. Chem.

    (1987)
  • A. Hall et al.

    J. Biol. Chem.

    (1986)
  • S. Kuroda et al.

    Biochem. Biophys. Res. Commun.

    (1989)

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    Copyright © 1991 Published by Elsevier B.V.