title: Enhanced phosphodiesteratic breakdown and turnover of phosphoinositides during reperfusion of ischemic rat heart.
abstract: In this study, we examined phosphoinositide metabolism during ischemia and reperfusion using an isolated and perfused rat heart. When myocardial phosphoinositides were prelabeled with [3H]inositol, reperfusion after 30 minutes of normothermic global ischemia resulted in significant accumulations of radiolabeled inositol phosphate, inositol bisphosphate, and inositol trisphosphate. Isotopic incorporation of [3H]inositol into phosphatidylinositol, phosphatidylinositol-4-phosphate, and phosphatidylinositol-4,5-bisphosphate was increased significantly in the heart reperfused with [3H]inositol after 30 minutes of ischemia compared with that perfused with [3H]inositol after 30 minutes of nonischemic perfusion. However, isotopic incorporation of [3H]glycerol into diacylglycerol, phosphatidic acid, and all of the three phosphoinositides was diminished in the reperfused hearts. Reperfusion of the ischemic heart prelabeled with [14C]arachidonic acid resulted in significant increases in [14C]diacylglycerol and [14C]phosphatidic acid. The enhanced accumulations of [3H]inositol phosphates during reperfusion were not affected by treatment with prazosin plus atropine or indomethacin, but were inhibited by hypoxic reperfusion, reperfusion with Ca2+-free buffer, or by mepacrine. These results suggest that myocardial reperfusion stimulates phosphodiesteratic breakdown and turnover of phosphoinositides, and increased Ca2+ influx caused by reperfusion may be involved in the mechanism of stimulation of phosphatidylinositol-specific phospholipase C activity in the rat heart.
authors.affiliation: Kansai Medical University, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Otani
authors.forename: M R
authors.initials: MR
authors.lastname: Prasad
authors.forename: R M
authors.initials: RM
authors.lastname: Engelman
authors.forename: H
authors.initials: H
authors.lastname: Otani
authors.forename: G A
authors.initials: GA
authors.lastname: Cordis
authors.forename: D K
authors.initials: DK
authors.lastname: Das
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D015424:Reperfusion
chemical_list: D010716:Phosphatidylinositols; D007294:Inositol; D002118:Calcium