Journal article
Reduced Adenosine A sub 1 Receptor and G sub alpha Protein Coupling in Rat Ventricular Myocardium During Aging
Circulation research, Vol.81(6), pp.1065-1071
Dec 1997
Abstract
Adenosine A1 receptor (A1-AdoR) function in rat ventricles has previously been shown to decrease with age. In the present study, using the ligand [sup 3 H]8-cyclopentyl-1,3-dipropylxanthine ([sup 3 H]DPCPX) and coimmunoprecipitation of A1-AdoRs with their associated G proteins, we determined the specific binding of A1-AdoR and A1-AdoR/G protein coupling in ventricular myocardium of 6- to 24-month-old Fischer 344 rats. The densities (Bmax) of A1-AdoRs were 5.8 +/- 0.8 fmol/mg protein in 6-month-old rats and 6.1 +/- 1.4 fmol/mg protein in 24-month-old rats, and the dissociation constants (Kd) were 0.32 +/- 0.04 nmol/L in 6-month-old rats and 0.34 +/- 0.05 nmol/L in 24-month-old rats (P>.05). Analysis of the dose-dependent displacement of [sup 3 H]DPCPX binding by the selective A1-receptor agonist, N-p-sulfophenyladenosine (SPA), yielded two affinity binding sites in both 6- and 24-month-old rats. However, the proportion of high-affinity A1-AdoRs was significantly lower in 24-month-old rats (23.5%) compared with 6-month-old rats (54.9%) (P<.05). In solubilized ventricular membranes, specific [sup 3 H]DPCPX binding sites were detected in immunoprecipitates of Galpha i3 and Galpha o antisera but not with antibodies for other Galpha proteins. The basal coimmunoprecipitation of A1-AdoR with Galpha i3 and Galpha o proteins decreased by 22% and 21%, respectively, in ventricular membranes of 24-month-old rats compared with that in 6-month-old animals. A1-AdoR stimulation with SPA increased the coprecipitation of A1-AdoR with Galpha i3 and Galpha o proteins by 287% and 245%, respectively, in 6-month-old rats but only by 129% and 140%, respectively, in 24-month-old rats (P<.01). In the absence of changes in A sub 1-AdoR density and Galpha protein levels, an agerelated decline in high-affinity A1-AdoR binding sites and a reduction in the association of A1-AdoR with Galpha proteins suggest that the age-related decrease in ventricular A1-AdoR-mediated response is related to a reduction in the coupling between A1-AdoR and their G proteins. (Circulation Research. 1997;81:1065-1071)
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Details
- Title
- Reduced Adenosine A sub 1 Receptor and G sub alpha Protein Coupling in Rat Ventricular Myocardium During Aging
- Creators
- Guoping CaiHoau-Yan WangErhe GaoJoel HorwitzDavid L SnyderAmir PellegJay RobertsEitan Friedman
- Publication Details
- Circulation research, Vol.81(6), pp.1065-1071
- Publisher
- American Heart Association, Inc
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Identifiers
- 991020531975404721