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

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Abstract
In the present work we studied the pharmacological profile of adenosine receptors in guinea pig atria by investigating the effect of different adenosine analogues on86Rb+-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 of86Rb+-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-ethylcarboxamidoadenosine (NECA), and S-N6-phenylisopropyladenosine (S-PIA) were 0.10, 0.14, 0.24 and 12.9 μM, 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.