Adenosine modulates beta-adrenergic signal transduction in guinea-pig heart ventricular membranes.

Abstract:

: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.

journal_name

J Mol Cell Cardiol

authors

Romano FD,Dobson JG Jr

doi

10.1016/0022-2828(90)90981-7

subject

Has Abstract

pub_date

1990-12-01 00:00:00

pages

1359-70

issue

12

eissn

0022-2828

issn

1095-8584

pii

0022-2828(90)90981-7

journal_volume

22

pub_type

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