Adenosine receptors mediating cardiac depression

Several adenosine analogs were evaluated for their effects on rate and contractility in guinea pig isolated atria. Among adenosine agonists, (?)-N-(1-methyl-2-phenylethyl) adenosine (?-phenylisopropyladenosine; ?-PIA) and N-cyclohexyladenosine (CHA), decreased rate and force at nanomolar concentrations, whereas 2-chloroadenosine, N, N-dimethyladenosine (N⁶-dimetyl-adenosine) and (+)-N-(1-methyl-2-phenylethyl) adenosine (d-phenyl-isopropyladenosine; d-PIA) were less potent cardiac depressants. The degree and order of potency of these agonists suggest that the cardiac depressant effects of adenosine are mediated via A₁-receptors. The cardiac depressant effects of CHA and ?-PIA were antagonized by theophylline and 1,3-diethyl-8-phenylxanthine (DPX).