Characterization of the K(+)-channel-coupled adenosine receptor in guinea pig atria.

In the present work we studied the pharmacological profile of adenosine receptors in guinea pig atria by investigating the effect of different adenosine analogues on 86Rb(+)-efflux from isolated left atria and on binding of the antagonist radioligand 8-cyclopentyl-1,3-[3H]dipropylxanthine [( 3H]DPCPX) to atrial membrane preparations. The rate of 86Rb(+)-efflux was increased twofold by the maximally effective concentrations of adenosine receptor agonists. The EC50-values for 2-chloro-N6-cyclopentyladenosine (CCPA), R-N6-phenylisopropyladenosine (R-PIA), 5'-N-ethylcarboxamidosadenosine (NECA), and S-N6-phenylisopropyladenosine (S-PIA) were 0.10, 0.14, 0.24 and 12.9 microM, respectively. DPCPX shifted the R-PIA concentration-response curve to the right in a concentration-dependent manner with a KB-value of 8.1 nM, indicating competitive antagonism. [3H]DPCPX showed a saturable binding to atrial membranes with a Bmax-value of 227 fmol/mg protein and a KD-value of 1.3 nM. Competition experiments showed a similar potency for the three agonists CCPA, R-PIA and NECA. S-PIA is 200 times less potent than R-PIA. Our results suggest that the K+ channel-coupled adenosine receptor in guinea pig atria is of an A1 subtype.