Cardioprotective effects of 2-octynyladenosine (YT-146) in ischemic/reperfused rat hearts.
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.
Drug Research Department, Fukushima Research Laboratories, Toa Eiyo Ltd., 1 Tanaka, Iizaka, Fukushima 960-0280, Japan. sasamori.jun@toaeiyo.co.jp
Jun
J
Sasamori
Kazuyuki
K
Aihara
Takehiro
T
Uchibori
Atsuo
A
Takahashi
Satoshi
S
Takeo
Kouichi
K
Tanonaka
D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000480:Alkynes / Q000627:therapeutic use*; D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D015425:Myocardial Reperfusion / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000480:Alkynes; D002316:Cardiotonic Agents; C070494:YT 146; D000241:Adenosine