Although lysophosphatidylcholine (lyso-PtdCho) accumulates in the sarcolemmal (SL) membrane and alters its function during myocardial ischemia and diabetic cardiomyopathy, the effects of lyso-PtdCho on SL signalling processes have not yet been investigated. The present study was carried out to examine the actions of lyso-PtdCho on the rat heart SL membrane enzymes involved in the phosphoinositide pathway. Different lyso-PtdCho species (10 to 200 μM) inhibited the activities of both phosphatidylinositol kinase and phosphatidylinositol-4-phosphate kinase in the SL membrane in a concentration-dependent manner. The inhibitory potency of lyso-PtdCho compounds for phosphatidylinositol kinase was lyso-PtdCho plasmalogen > 1- oleoyl-lyso-PtdCho > 1-stearoyl-lyso-PtdCho > 1-palmitoyl-lyso-PtdCho, and that for phosphatidylinositol-4-phosphate kinase was lyso-PtdCho plasmalogen > 1-oleoyl-lyso-PtdCho > 1-palmitoyl-lyso-PtdCho > 1-steamyl-lyso-PtdCho. The inhibitory effect of lyso-PtdCho on phosphatidylinositol-4-phosphate kinase was greater than that on phosphatidylinositol kinase. Lyso-PtdCho structural analogues, such as phosphatidylcholine, lysophosphatidic acid, lysophosphatidylethanolamine, L-α-glycerophosphate, oleate and phosphorylcholine, did hot affect the phosphoinositide kinases, suggesting that the intact structure of lyso-PtdCho was required for the inhibition of the kinases. The detrimental action of lyso-PtdCho on PtdIns kinase was potentiated by acidosis. Unlike Ca2+, ATP (0.1 and 4 mM) increased lyso- PtdCho-induced deactivation of the kinases. Both enzyme activities were found to be depressed in the ischemic-reperfused or diabetic hearts. None of the tested lyso-PtdCho species altered phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) hydrolysis by SL phospholipase C. These results indicate that accumulation of lyso-PtdCho in the SL membrane under pathological conditions may diminish the availability of the PtdIns(4,5)P2substrate for the production of second messengers by receptor-linked phospholipase C.
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