Evidence for an Ax‐adenosine receptor in the guinea‐pig atrium

Abstract

1 The purpose of this study was to determine whether the adenosine receptor that mediates a decrease in the force of contraction of the guinea-pig atrium is of the A₁- or A₂-sub-type. 2 Concentration-response curves to adenosine and a number of 5′- and N⁶-substituted analogues were constructed and the order of potency of the purines was: 5′-N-cyclopropylcarboxamide adenosine (NCPCA) = 5′-N-ethylcarboxamide adenosine (NECA) >N⁶cyclohexyladenosine (CHA) > L-N⁶-phenylisopropyl adenosine (l-PIA) = 2-chloroadenosine > adenosine > D-N⁶-phenylisopropyl adenosine (d-PIA). 3 The difference in potency between the stereoisomers d- and l-PIA was over 100 fold. 4 The adenosine transport inhibitor, dipyridamole, potentiated submaximal responses to adenosine but had no significant effect on those evoked by the other purines. 5 Theophylline antagonized responses evoked by all purines, and with d-PIA revealed a positive inotropic effect that was abolished by atenolol. 6 The results indicate the existence of an adenosine Ai-receptor in the guinea-pig atrium.