Involvement of PL-D in the alternate signal tranduction pathway of macrophages induced by an exernal stimulus

The alternate pathway of signal transduction via hydrolysis of phosphatidyl choline, the major cellular phospholipid, has been investigated in murine p eritoneal macrophages. A sustained formation of diacylglycerol, is preceded by an enhanced production of phosphatidic acid, when the macrophages were given a stimulus with 12-O-tetradecanoyl phorbol-13-acetate for sixty minut es. Production of choline and choline metabolites are significantly increas ed too. Propranolol, which inhibits phosphatidate phosphohydrolase, the enz yme responsible for conversion of phosphatidic acid to diacylglycerol, can effectively block the formation of diacylglycerol. Inhibition of protein ki nase C either by its inhibitors, staurosporine and H-7 or by depletion, app arently affect the generation of the lipid products. Moreover, based on the results of transphosphatidylation reaction, involvement of a phospholipase D in the phosphatidylcholine-hydrolytic pathway in macrophages is predicte d. These observations support the view that probably the phorbol ester acti ng directly on protein kinase C of the macrophages activate their phosphati dylcholine-specific phospholipase D to allow a steady generation of second messengers, to enable them to participate in the cell signalling process in a more efficient manner than those generated in the phosphoinositide pathw ay of signal transduction.