Inhibitory Effects of KW-3902, a Selective Adenosine A1-Receptor Antagonist, on the Adenosine-Induced Shortening of Action Potential Duration in Guinea Pig Atrial Muscles

Abstract

We investigated the effects of KW-3902 (8-(noradamantan-3-yl)-1,3- dipropylxanthine), a newly-synthesized selective adenosine A1-receptor antagonist, on the shortening of action potential duration (APD) in guinea pig atria exposed to adenosine. The APD shortening by adenosine was inhibited by KW-3902 at higher than 10(-8) M, but not by 10(-5) M of KF17837, an adenosine A2-receptor antagonist. These results support the notion that the APD shortening by adenosine in atria is mediated via adenosine A1-receptors. The potency of KW-3902 in antagonizing the APD-shortening were similar to those in antagonizing the negative inotropic and chronotropic action of adenosine in the isolated right atria, suggesting that these responses to adenosine are mediated via the receptors of the same type.