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

Summary

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.