Cardiac adenylate cyclase: Kinetics of synergistic activation by guanosine-5′-triphosphate (GTP) and glucagon

Robert F. Fricke, Sherry F. Queener, Charles M. Clark

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Kinetic analysis of cardiac adenylate cyclase activation by GTP and glucagon has been performed. The maximal stimulation produced by 1 mm GTP or 10 μm glucagon alone was approximately 2-fold over basal activity; with both GTP and glucagon, activity was synergistically increased 5-fold over basal. The apparent KD for activation of cardiac adenylate cyclase by glucagon was 0.16 μm and was not altered by maximal or submaximal concentrations of GTP. The apparent KD for activation by GTP was 4.18 μm; this value was not altered by maximal or submaximal concentrations of glucagon. The apparent Km values for MgATP and apparent Vm values were determined in the basal state and in the presence of 10 μm glucagon and various fixed levels of GTP (none, 1, 10, and 100 μm) and in the presence of 1 mm GTP and various fixed concentrations of glucagon (none, 0.1, 1, 10 μm). No difference in the apparent Km for the substrate was determined under these various conditions (mean of all determination = 0.280 ± 0.01 mm). The apparent Vm values, however, increased greatly in the presence of the two effectors. The Vm values determined under basal conditions or with GTP alone or glucagon alone were 51 ± 3, 67 ± 3, and 79 ± 3 pmol/mg protein/min, respectively. At saturating levels of both GTP and glucagon the Vm value was 255 ± 11 pmol/mg protein/min. The kinetic data for the activation of the cardiac adenylate cyclase by GTP and glucagon were analyzed further using a rate equation which expresses the high degree of synergism between GTP and glucagon in terms of interaction constants.

Original languageEnglish (US)
Pages (from-to)595-608
Number of pages14
JournalJournal of Molecular and Cellular Cardiology
Volume12
Issue number6
DOIs
StatePublished - Jun 1980

Keywords

  • Adenylate cyclase
  • Association constants for activation
  • Cardiac membrane
  • Glucagon
  • Guanyl nucleotides
  • Kinetics of adenylate cyclase

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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