Adenosine A1 and A2A receptor effects on G-protein cycling in beta-adrenergic stimulated ventricular membranes
Department of Physiology
Adenosine; Adenylate Cyclase; Adrenergic beta-Agonists; Animals; GTP-Binding Proteins; Guanosine Diphosphate; Heart Ventricles; Isoproterenol; Membrane Proteins; Membranes; Phenethylamines; Precipitin Tests; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A1; Receptors, Adenosine A2
Cardiovascular Diseases | Cellular and Molecular Physiology | Physiology
In the heart beta1-adrenergic (beta1R) and adenosine A1 (A1R) and A2A (A2AR) receptors modulate contractile and metabolic function. The interaction between these receptors was investigated at the level of G-protein cycling by determining the effect of receptor agonists on the binding of GTP to G-proteins and displacement of G alpha-subunit-bound GDP by GTP. Crude membranes from rat heart or brain were stimulated by agonists for beta1R (isoproterenol; ISO), A1R (chlorocyclopentyladenosine, CCPA) and A2AR (CGS-21680; CGS). GTP binding to membranes was increased by ISO (17%), CCPA (6%) and CGS (12%). Binding values observed with incubation using ISO and CCPA together were significantly less than values obtained by the incubation of individual agents alone. With ISO, GTP binding to G alpha(s) subunits as determined by immunoprecipitation was increased 79% in heart and 87% in brain. These increases were attenuated by CCPA, an effect that was inhibited by CGS. GDP release by membranes was increased 6.9% and 4.6% by ISO and CCPA, respectively. After co-incubation of these agonists, release was increased less than determined by the addition of the individual agent responses. CGS inhibited the reduced release caused by of CCPA. Adenylyl cyclase activity stimulated by ISO was attenuated 33% by CCPA, an effect inhibited by CGS. Together, these results indicate that A1R exert an antiadrenergic action at the level of beta1R stimulated G(s)-protein cycling and that A2AR reduce this action.
DOI of Published Version
J Cell Physiol. 2007 Dec;213(3):785-92. Link to article on publisher's site
Journal of cellular physiology
Fenton, Richard A. and Dobson, James G. Jr., "Adenosine A1 and A2A receptor effects on G-protein cycling in beta-adrenergic stimulated ventricular membranes" (2007). Physiology Publications and Presentations. 64.