November 1, 1989Open Access
View Full PaperCharacterization of A1 adenosine receptors in atrial and ventricular myocardium from diseased human hearts.
Key Result
A1 adenosine receptors exist in human myocardium, with similar binding properties but 1.7 times greater receptor density in atrial versus ventricular tissue (26.9 vs 16.2 fmol/mg protein).
Structured PICO
P
Population
In vitro study characterizing A1 adenosine receptors in atrial and ventricular myocardium from diseased human hearts.
I
Intervention
Adenosine and adenosine receptor agonists/antagonists (8-phenyltheophylline, DPCPX, R-PIA, S-PIA, NECA)
O
Outcome
Characterization of A1 adenosine receptors (inotropic effects, binding affinity, and receptor density)surrogate
A1 adenosine receptors exist in human myocardium with similar binding properties but higher density in atrial compared to ventricular tissue, suggesting coupling to different effectors.
Abstract
The purpose of the present study was to characterize adenosine receptors in human atrial and ventricular myocardium. In isolated electrically driven preparations, adenosine produced "direct" negative inotropic effects in atrial myocardium (AT). In ventricular myocardium (VE), it only had negative inotropic properties when force of contraction had been stimulated with isoprenaline ("indirect" effect), but it has no inotropic effect alone. The adenosine receptor antagonist 8-phenyltheophylline antagonized the "direct" and "indirect" effects; these findings indicated that both effects were mediated by adenosine receptors. In cardiac membranes from human AT and VE, adenosine receptors were characterized with 3H-8-cyclopentyl-1,3-dipropylxanthine (DPCPX) binding. The effects of agonists R-(-)-N6-phenylisopropyladenosine (R-PIA), S-(+)-N6-phenylisopropyladenosine (S-PIA), and 5'-(N-ethylcarboxamido) adenosine (NECA) and the effects of guanine nucleotides Gpp(NH)p were studied also. The antagonist affinities as judged from the apparent affinity, Kd, of 3HDPCPX were similar in AT (2.2 nmol/l; 95% confidence limits, 1.4-3.7) and VE (1.8 nmol/l; 95% confidence limits, 1.0-3.0). The number of adenosine receptors was 1.7 times greater in AT (26.9 +/- 2.33 fmol/mg protein; n = 5) than in VE (16.2 +/- 2.3 fmol/mg protein; n = 5). High and low affinity states of adenosine receptors evaluated with the influence of Gpp(NH)p on agonist competition with R-PIA were similar in AT or VE. The rank orders of potency for agonists (R-PIA greater than S-PIA greater than NECA) and antagonists (DPCPX greater than 8-phenyltheophylline greater than theophylline) were characteristic for the A1 receptor subtype. It is concluded that A1 adenosine receptors exist in the human myocardium. Since binding properties were similar in AT and VE, the same A1 adenosine receptor probably couples to different effectors in a similar guanine nucleotide-dependent way. 3HDPCPX is the first radiolabeled antagonist ligand that allows detection of A1 adenosine receptors and their coupling in the human myocardium.