Calcium-Phosphatidylinositol Interactions in Secretory Cells and the Role of Arachidonic Acid

Abstract

Since secretagogues express their actions by increasing \(C{{a}^{{{{2}^{ + }}}}}\) availability and promoting membrane phospholipid turnover, the fundamental action of \(C{{a}^{{{{2}^{ + }}}}}\) in stimulus-secretion coupling may be uncovered by elucidating its interactions with membrane phospholipids. The turnover of arachidonoyl phosphatidylinositol (PI) triggered by the \(C{{a}^{{{{2}^{ + }}}}}\)-dependent activation of phospholipase A2 and followed by the reincorporation of fatty acid into lysophospholipids, appears to be one feature that secretory systems have in common. Stimulated arachidonic acid turnover in position 2 of PI has now been demonstrated in a number of secretory systems, including adrenal cortex, rabbit peritoneal neutrophils, and exocrine pancreas. The relevance of this reaction to secretory phenomena is indicated by its requirement for \(C{{a}^{{{{2}^{ + }}}}}\), its rapid onset, and dose-response curves that parallel those of the secretory response. One or another of the products of this deacylation-reacylation cycle, including arachidonic acid metabolites and/or lysophospholipids, may participate in the cellular processes that accompany the export of secretory product from the cell. Products of the activation of phospholipase C, including diacylglycerol and/or inositol phosphates, may also serve as second messengers. Insight into the nature of the interactions between phospholipases A2 and C with regard to their putative physiological roles should shed significant light on the vital control mechanisms that regulate the secretory process.