Diacylglycerol delays pH(i) overshoot after reperfusion and attenuates contracture in isolated, paced myocytes.
Although protein kinase C (PKC) plays a pivotal role in ischemic preconditioning, it is not clear what the end effector is that protects the myocardium. In isolated, paced (1.25 Hz, 36-37 degrees C) adult rat cardiomyocytes, the effects of PKC preactivation by diacylglycerol on cell motion, intracellular Ca(2+) concentration ([Ca(2+)](i); indo 1), and intracellular pH (pH(i); seminaphthorhodafluor-1) during simulated ischemia-reperfusion (I/R) were investigated. The degree of reperfusion-induced contracture was significantly attenuated in the myocytes pretreated with 10 microM 1, 2-dioctanoyl-sn-glycerol (DOG; n = 19) compared with the untreated myocytes (n = 23, P < 0.02). There were no differences in twitch amplitude, end-diastolic [Ca(2+)](i), or peak-systolic [Ca(2+)](i) during I/R between the DOG-pretreated and untreated myocytes. Although there were no differences in pH(i) during ischemia, the pH(i) overshoot during reperfusion was significantly delayed in the DOG-pretreated myocytes compared with the untreated myocytes (n = 17 for each, P < 0.01). Chelerythrine completely abolished the favorable effects of DOG on the reperfusion-induced contracture and the pH(i) overshoot. These data suggest that diacylglycerol attenuates I/R injury in isolated, paced cardiomyocytes, which may be related to the slower pH(i) overshoot during reperfusion.
Ito
K
K
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai 980-8574, Japan.
Kagaya
Y
Y
Ishizuka
T
T
Ito
N
N
Ishide
N
N
Shirato
K
K
D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D002118:Calcium / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D002469:Cell Separation; D003931:Diacetyl / Q000031:analogs & derivatives / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009994:Osmolar Concentration; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D000470:Alkaloids; D053119:Benzophenanthridines; D004075:Diglycerides; D004791:Enzyme Inhibitors; D010617:Phenanthridines; C044295:1,2-dioctanoylglycerol; C004717:diacetylmonoxime; D006859:Hydrogen; C016299:chelerythrine; D011493:Protein Kinase C; D003931:Diacetyl; D002118:Calcium