The present study was aimed at investigating the cardiac receptor subtypes involved in the cardioprotective effects of
2-octynyladenosine (YT-146), a novel
adenosine receptor (AR) agonist. Isolated rat hearts were perfused in the Langendorff manner, and the hearts were exposed to 30 minute of
ischemia followed by 60 minutes of reperfusion.
YT-146 was infused for 10 minutes just before
ischemia, and selective antagonists for AR subtypes were coadministered with
YT-146.
YT-146 (0.03–0.3 μM) dose dependently improved postischemic recovery of the left ventricular developed pressure (LVDP) of the ischemic/reperfused rat heart (maximum 59.7% ± 2.3% of the preischemic value). Coadministration of 8-(3-chlorostyryl)
caffeine (A(2A) AR antagonist),
alloxazine (A(2B)AR antagonist), or
MRS-1191 (A(3) AR antagonist) with
YT-146 failed to alter the cardioprotective effects of
YT-146, and their LVDP recoveries were 55.9% ± 5.1%, 52.1% ± 1.9%, and 47.5% ± 1.7%, respectively, at the end of the reperfusion. On the other hand, coadministration of
8-cyclopentyl-1,3-dipropylxanthine (A(1) AR antagonist) abolished the YT-146–induced enhancement of postischemic LVDP recovery (31.7% ± 4.6%). The
protein kinase C inhibitor
chelerythrine also abolished the YT-146–induced enhancement of postischemic LVDP recovery (22.2% ± 4.5%).
YT-146 has been known as an A(2) AR agonist, but our findings suggest that the cardioprotective effects of
YT-146 are exerted via cardiac A(1) AR, not A(2) AR, stimulation and the activation of
protein kinase C by preischemic treatment in isolated and
crystalloid-perfused rat hearts.