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Regulation of phosphatidylinositol turnover, calcium metabolism and enzyme secretion by phorbol dibutyrate in neutrophils
Author(s) -
Kramer Caroline M.,
Franson Richard C.,
Rubin Ronald P.
Publication year - 1984
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02534781
Subject(s) - phosphatidylinositol , phosphatidic acid , phorbol , arachidonic acid , protein kinase c , phospholipase d , phosphatidylethanolamine , medicine , endocrinology , diacylglycerol kinase , secretion , phospholipase c , phosphatidylserine , phosphatidylcholine , calcium , phospholipase a2 , second messenger system , chemistry , biology , biochemistry , phospholipid , receptor , enzyme , signal transduction , membrane
The action of the tumor promoter, phorbol 12,13‐dibutyrate (PDBu), on rabbit peritoneal and human neutrophils is associated with stimulation of 14 C‐arachidonic acid incorporation into phospholipids within 1–2 min. Stimulated 14 C‐arachidonate incorporation was relatively selective for phosphatidylinositol (PI) in rabbit neutrophils. In contrast, the secretory response of human neutrophils to PDBu coincided with stimulated label incorporation into phosphatidylserine (PS), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA) and PI. Significant increases in label incorporation were observed with PDBu concentrations as low as 2 nM, and the dose response of stimulated label incorporation paralleled that of evoked lysozyme secretion. A parallel, but partial, inhibition of PDBu‐stimulated PI labeling and enzyme release was observed after exposing rabbit neutrophils to calcium‐deprived medium, whereas calcium deprivation failed to significantly depress either of these stimulant actions of PDBu in human neutrophils. Further, in rabbit neutrophils PDBu elicited an increase in cell associated 45 Ca. However, PDBu was unable to promote the incorporation of 32 P orthophosphate into PI or enhance phospholipase A 2 activity in broken cells. These findings suggest that one expression of the interaction between phorbol esters and their receptors on neutrophils involves the turnover of arachidonic acid in phospholipids. This stimulated turnover of arachidonate may be a critical step in the cascade of events associated with neutrophil activation.