phosphatidylinositol-4-phosphate and Coronary-Disease

In this study the mass of polyphosphoinositides as well as the turnover of [3H]inositol phospholipids and [3H]inositol phosphates during ischaemia and short periods of reperfusion were studied in the isolated perfused rat heart. Since the phosphoinositides located within the sarcolemma are precursors for release of inositoltrisphosphate (InsP3) and diacylglycerol, sarcolemmal membranes (rather than whole tissue) isolated at the end of the experimental procedure, were used. Hearts were prelabelled with [3H]inositol and subsequently perfused with 10 mM LiCl to block the phosphatidylinositol (PI) pathway. The results showed that 20 min of global ischaemia depressed the amount of [3H]inositol present in both sarcolemmal phosphatidylinositol-4-phosphate (PI-4-P) and phsophatidylinositol-4,5-bisphosphate (PI-4,5-P2), as well as in the cytosolic [3H]inositol phosphates, [3H]InsP2 and [3H]InsP3. The mass of the sarcolemmal inositol phospholipids remained unchanged during ischaemia. Reperfusion caused an immediate (within 30 sec) increase in the amount of [3H]inositol in sarcolemmal PI, PI-4-P and PI-4,5-P2. PI-4-P levels showed a transient increase after 30 seconds postischaemic reperfusion, while the mass of the other sarcolemmal inositol phospholipids, PI and PI-4,5-P2, remained unchanged. [3H]InsP, [3H]InsP2 and [3H]InsP3 also increased significantly in comparison to ischaemic hearts after only 30 sec postischaemic reperfusion. In summary, the results obtained indicate inhibition of the PI pathway during ischaemia with an immediate significant stimulation upon reperfusion. In view of the capacity of InsP3 to mobilize Ca2+, the possibility exists that stimulation of this pathway during reperfusion may play a role in the intracellular Ca2+ overload, characteristic of postischaemic reperfusion.

Topics: Animals; Coronary Disease; Inositol Phosphates; Male; Myocardial Reperfusion; Myocardium; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositol Phosphates; Phosphatidylinositols; Rats; Rats, Inbred Strains; Sarcolemma