Adenosine modulates beta-adrenergic signal transduction in guinea-pig heart ventricular membranes
Department of Physiology
Adenosine; Adenosine Diphosphate Ribose; Adenylate Cyclase; Animals; Cell Membrane; Guanosine Diphosphate; Guanosine Triphosphate; Guinea Pigs; Heart Ventricles; Magnesium; Phenylisopropyladenosine; Radioligand Assay; Receptors, Adrenergic, beta; Receptors, Purinergic; Signal Transduction
Cardiovascular Diseases | Cellular and Molecular Physiology | Physiology
The mechanism of the antiadrenergic action of adenosine in the heart was investigated by examining the effects of phenylisopropyladenosine (PIA), an adenosine A1 receptor agonist, on beta-adrenergic receptor and non-receptor elicited increases in adenylyl cyclase activity of guinea-pig ventricular membranes. These membranes contained adenosine A1 receptors (approximately 80 fmol/mg) and at least one ADP-ribosylated G protein with a molecular weight of approximately 40 kDa. PIA attenuated isoproterenol-enhanced adenylyl cyclase activity and [3H]GDP release in this membrane preparation. However, PIA had no significant effect on GPP(NP)P or forskolin activated adenylyl cyclase. Additionally, PIA did not change the sensitivity of the cyclase to either magnesium or GTP in these membranes. The inhibition of isoproterenol-enhanced activity appeared to be dependent on the activation state of the enzyme such that the degree of PIA inhibition decreased with increasing isoproterenol concentration. These data suggest that adenosine inhibition of catecholamine-stimulated adenylyl cyclase activity occurs predominantly by modulating beta-adrenergic receptor signal transduction and that subunits of Gi may be involved in this action.
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Citation: J Mol Cell Cardiol. 1990 Dec;22(12):1359-70.
Romano, Fred D. and Dobson, James G. Jr., "Adenosine modulates beta-adrenergic signal transduction in guinea-pig heart ventricular membranes" (1990). Physiology Publications and Presentations. 46.