Title

The adenosine Ri agonist, phenylisopropyladenosine, reduces high affinity isoproterenol binding to the beta-adrenergic receptor of rat myocardial membranes

UMMS Affiliation

Department of Physiology

Date

1-1988

Document Type

Article

Subjects

Adenosine; Adenylate Cyclase; Animals; Data Interpretation, Statistical; Heart; Isoproterenol; Male; Membranes; Myocardium; Phenylisopropyladenosine; Rats; Rats, Inbred Strains; Receptors, Adrenergic, beta

Abstract

Adenosine attenuates beta-adrenergic receptor mediated activation of adenylate cyclase in myocardial membranes via adenosine Ri receptors. The effects of adenosine analogs on the binding characteristics of beta-adrenergic receptors were examined in the present study utilizing rat ventricular membranes treated with adenosine deaminase. In 125I-cyanopindolol/isoproterenol competitive binding experiments phenylisopropyladenosine (PIA) significantly increased the IC50 for isoproterenol from 48 +/- 6 nM to 140 +/- 48 nM and steepened the slope of the competition curves from -0.56 +/- 0.03 to -0.90 +/- 0.21. Computer analysis of these curves indicated that binding of isoproterenol to the high affinity state of the beta-adrenergic receptor was eliminated in the presence of PIA. PIA had no effects in the presence of GPP(NH)P. 2-chloroadenosine, a less specific Ri agonist, caused smaller increases in IC50 and slope, without significantly affecting high affinity binding. 2',5'-dideoxyadenosine, a P-site agonist, had no significant effects on isoproterenol binding. During the time course of the competitive binding experiments the membranes displayed isoproterenol-sensitive adenylate cyclase activity in the absence of added GTP. These data suggest that adenosine attenuates catecholamine-induced activation of adenylate cyclase via Ri receptors by decreasing the ability of beta-adrenergic agonists to promote the formation of a high affinity complex composed of the agonist, receptor and stimulatory guanine nucleotide binding protein.

Rights and Permissions

Citation: Second Messengers Phosphoproteins. 1988;12(1):29-43.

Related Resources

Link to article in PubMed

PubMed ID

2848121

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