Pharmacological characterization of A1 adenosine receptors in isolated rat ventricular myocytes.

The aim of the present study was the characterization of adenosine receptors in isolated rat ventricular myocytes. The cAMP-levels of rat ventricular myocytes in the presence of 1 mumol/l isoprenaline were reduced by up to 48% by adenosine analogues; the rank order of potency was: R-N6-phenylisopropyladenosine (IC50 60 nmol/l), 5'-N-ethylcarboxamidoadenosine (IC50 360 nmol/l) and S-N6-phenylisopropyladenosine (IC50 16 mumol/l). The adenosine receptor antagonist XAC ("xanthine amine congener") antagonized the effect of R-N6-phenylisopropyladenosine in a concentration-dependent manner with a Ki-value of 20 nmol/l. The A1 receptor-selective radioligand R-N6-125I-p-hydroxyphenylisopropyladenosine bound to membranes prepared from rat ventricular myocytes in a saturable manner with a Bmax of 17.7 fmol/mg protein and a KD-value of 1.1 nmol/l. Adenosine analogues competed for the binding with the same rank order of potency as for the inhibition of the isoprenaline-induced cAMP-increase. GTP inhibited radioligand binding with an IC50-value of 73 mumol/l. These results suggest the presence of A1 adenosine receptors on rat ventricular myocytes, which mediate an inhibition of adenylate cyclase. The receptors may be responsible for the effects of adenosine and its analogues on the heart.