Occurrence and functions of the phosphatidylinositol cycle in the myocardium

In the last decade a great deal of attention was awarded to a signal transduction pathway which is utilized primarily by Ca²⁺ mobilizing signal molecules and which involves the hydrolysis of a quantitatively minor phospholipid, phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P₂) by a PtdIns-specific phospholipase C (PLC). The evidence for the existence of receptor-mediated GTP binding protein-coupled PLC in myocardium and its possible functions are briefly summarized. The minireview is concentrated on the following aspects: 1) cellular localization and synthesis of polyphospho-PtdIns from PtdIns, 2) desensitization of the ₁-adrenergic agonist and endothelin-1 mediated PtdIns responses, 3) oscillatory Ca²⁺ transients initiated by Ptdlns(4,5)P₂ hydrolysis, 4) polyunsaturated fatty acids as constituents of polyphospho-PtdIns and of the protein kinase C activator 1,2-diacylglycerol (DAG), 5) source other than Ptdlns(4,5)P₂ contributing to the stimulated DAG, 6) role of the PtdIns pathway in cardiomyocyte growth and gene expression during the hypertrophic response. (Mol Cell Biochem116: 59–67, 1992)Abbreviations Phosphatidylinositol 4,5-bisphosphate PtdIns(4,5)P₂ - Phosphatidylinositol 4-monophosphate PtdIns(4)P₄ - Phosphatidylinositol PtdIns - Inositol 1,4,5-triphosphate Ins(1,4,5)P₃ - Inositol 1,3,4,5-tetrakisphosphate Ins(1,3,4,5)P₄ - Inositol 1-monophosphate Ins(1)P - Inositol 1,4-bisphosphate Ins(1,4)P₂ - Inositol Ins - Inositolphosphates InsP_n - Guanine 5'-triphosphate GTP - GTP binding protein G-protein - Phosphatidylinositolspecific phospholipase C PLC - Protein kinase C PKC - 1,2-Diacylglycerol DAG - Monoacylglycerol MAG - cytidyldiphoshate-diacylglycerol CDP-DAG - Sarcolemma SL - Sarcoplasmic reticulum SR - Stearic acid 18:0 - Polyunsaturated fatty acids PUFA - Arachidonic acid 20:4n-6 - Linoleic acid 18:2n-6 - Eicosapentaenoic acid 20:5n-3 - Docosahexaenoic acid 22:6n-3 - Phosphatidic acid PtdOH - Phospholipase D PLD - Phosphatidylcholine PtdChol