Tohoku J. Exp. Med., 1999, 188 (1)

Similarity and Dissimilarity in Mode and Mechanism of Action between YT-146, a Selective Adenosine Receptor A2 Agonist, and Adenosine in Isolated Canine Hearts

FUMIYA YONEYAMA, KAZUYUKI AIHARA,1 KENTARO KOGI,1 KEISUKE SATOH and NORIO TAIRA

Department of Pharmacology, Tohoku University School of Medicine, Sendai 980-8575, and 1Toa Eiyo, Ltd., Iizaka, Fukushima 960-0280

  • To elucidate the differences in mode and mechanism of action between YT-146, a highly selective adenosine A2 receptor agonist, and adenosine, we compared their effects on coronary circulation and myocardium and modifications of these effects by glibenclamide, a blocker of ATP-sensitive potassium (K) channels, in three kinds of isolated, blood-perfused canine heart preparations. YT-146 and adenosine were injected i.a. In all preparations both YT-146 and adenosine increased coronary blood flow and in this respect YT-146 was about 5 times as potent as adenosine. The increase in blood flow caused by adenosine was transient, whereas that produced by YT-146 was biphasic; the transient increase was followed by a sustained one. In isolated, blood-perfused sinoatrial (SA) node preparations, YT-146 failed to affect sinus rate, whereas adenosine reduced sinus rate by about 38% at its maximum effect. In isolated, blood-perfused atrioventricular (AV) node preparations, when injected into the artery supplying the AV node, YT-146 exerted no effect on AV conduction time, whereas adenosine prolonged AV conduction time by about 17% at the maximum effect. In isolated, blood-perfused papillary muscle preparations, the force of contraction was affected by neither YT-146 nor adenosine. In the same preparations the effect of YT-146 in increasing coronary blood flow was antagonized by glibenclamide in such a manner that the maximum increase was suppressed, but that of adenosine was not. Reactive hyperemia induced by ischemia for 30 seconds was not affected by glibenclamide. These results suggest that although both YT-146 and adenosine produce an increase in coronary blood flow via adenosine A2 receptors, the opening of ATP- or glibenclamide-sensitive K channels is involved in the action of the former, but scarcely in the action of the latter. The opening of ATP- or glibenclamide-sensitive K-channels is less likely involved in reactive hyperemia.
    Key words--- adenosine A2 receptor agonist; ATP-sensitive K-channel; coronary blood flow; YT-146
    © 1999 Tohoku University Medical Press

    Tohoku J. Exp. Med., 1999, 188, 31-45
    Address for reprints: Fumiya Yoneyama, Toa Eiyo, Ltd., 1 Tanaka, Yuno, Iizaka, Fukushima 960-0280, Japan.

    Back to CONTENTS.