Differential activation of phosphatidylinositol deacylation and a pathway via diphosphoinositide in macrophages responding to zymosan and ionophore A23187.
The inositol phospholipids of peritoneal macrophages were prelabeled with [3H]inositol to enable studies on the enzymatic mechanisms of stimulus-induced phosphatidylinositol breakdown. Ionophore A23187 induced a rapid breakdown of phosphatidylinositol in the presence of Ca2+ with 25% loss occurring within 5 min. The main water-soluble product of this breakdown was identified as inositol diphosphate. Since the accumulation of inositol diphosphate far exceeded the concomitant decrease in polyphosphoinositides, an increased phosphorylation of phosphatidylinositol must have preceded, or accompanied, the degradation of diphosphoinositide. The degradation of phosphatidylinositol induced by A23187 was shown to be strictly dependent on Ca2+. The monovalent cation ionophore monensin and platelet-activating factor increased the level of diphosphoinositide but caused no net degradation of inositol phospholipids. The same effect was seen with ionophore A23187 in the absence of Ca2+. Zymosan particles also induced extensive degradation of phosphatidylinositol. Products of phosphodiesterase-catalyzed cleavage of inositol lipids were observed, but the pathway of deacylation dominated as evidenced by the accumulation of lysophosphatidylinositol and glycerophosphoinositol. Deacylation was also enhanced in response to concanavalin A. Thus, in mouse peritoneal macrophages phosphatidylinositol breakdown occurred primarily by deacylation or via diphosphoinositide, depending on the stimulus, rather than through a phosphatidylinositol phosphodiesterase reaction.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008985:Monensin / Q000494:pharmacology; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology*
D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; C023687:diphosphoinositides; D000001:Calcimycin; D015054:Zymosan; D008985:Monensin; D002118:Calcium