Reperfusion following myocardial ischaemia enhances inositol phosphate release in the isolated perfused rat heart.
1. Global myocardial ischaemia (MI) for periods greater than 5 min caused an inhibition of phosphatidylinositol specific phospholipase C (PtdIns-PLC) activity. 2. Two min reperfusion following a 20 min MI period, a time point associated with reperfusion-induced arrhythmias, resulted in an activation of PtdIns-PLC activity, dependent on endogenous noradrenaline and mediated via alpha 1-adrenoceptors. 3. This 2 min reperfusion response, in contrast to healthy myocardium, resulted in: (i) enhanced PtdIns-PLC activity; (ii) increased sensitivity to endogenous noradrenaline; (iii) rapid increases in inositol(1,4,5)trisphosphate (Ins(1,4,5)P3); and (iv) PLC hydrolysis primarily of PtdIns(4,5)P2, such that the majority of InsP isomers derive from Ins(1,4,5)P3. 4. Together, these data suggest a functional role for Ins(1,4,5)P3 under post-ischaemic reperfusion conditions, and provide a possible link between alpha 1-adrenoceptor stimulation of the PtdIns turnover pathway and reperfusion injury.
Cellular Biochemistry Laboratory, Baker Medical Research Institute, Prahran, Victoria, Australia.
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Anderson
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Dart
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Woodcock
D000818:Animals; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D007295:Inositol Phosphates; D015544:Inositol 1,4,5-Trisphosphate; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D009355:Neomycin; D009638:Norepinephrine