Evidence for a role of phosphatidylinositol turnover in stimulus–secretion coupling. Studies with rat peritoneal mast cells

Abstract

Histamine secretion and phosphatidylinositol turnover were compared in antigen-sensitized rat peritoneal mast cells stimulated with a number of different ligands. A small and variable increase in the incorporation of [(32)P]P(i) and of [(3)H]inositol into phosphatidylinositol was observed when the cells were treated with immunoglobulin E-directed ligands (antigens and concanavalin A), and this was accompanied by a low amount of secretion (<10% of total cell histamine). In the presence of added phosphatidylserine, the addition of immunoglobulin E-directed ligands invariably led to an enhanced rate (approx. 4-fold) of labelling of phosphatidylinositol and, in the presence of Ca(2+), this was accompanied by the secretion of histamine. The labelling of phosphatidylinositol and histamine secretion were also stimulated by chymotrypsin and compound 48/80. Whereas the phosphatidylinositol response did not require the presence of extracellular Ca(2+), the secretion of histamine was either enhanced or dependent on extracellular Ca(2+) (depending on the ligand used). The dependence on ligand concentration for the phosphatidylinositol response and histamine secretion were similar. The increased isotopic incorporation into phosphatidylinositol continued for about 1h although histamine secretion (elicited with concanavalin A) stopped within 2min. These results support the proposition that metabolic events involving phosphatidylinositol play a necessary intermediate role in the regulation of Ca(2+) channels by ligand-activated receptors.

Elimination of plasma membrane phosphatidylinositol (4,5)-bisphosphate is required for exocytosis from mast cells

“…Second, there is an obligate role for DAG generation during exocytosis in neurons to facilitate activation of Munc13 (Brose and Rosenmund, 2002). Third, activation of exocytosis stimulates PLC in a number of cell types, including adrenal chromaffin cells (Whitaker, 1985) and RPMCs (Cockcroft and Gomperts, 1979). Finally, U73-122 and isoform-specific PLC antibodies were found to inhibit chromaffin-cell exocytosis (O'Connell et al, 2003).…”

Activation and inhibition of calcium‐dependent histamine secretion by ATP ions applied to rat mast cells.

“…The activation involves an increase in the rate of turnover of the phosphatidylinositol cycle (Cockcroft & Gomperts, 1979a) which probably precedes and may regulate a subsequent flux of Ca2+ into the cytosol (Foreman, Hallett & Mongar, 1977). This triggers the exocytotic process which leads to the release of histamine (Gomperts, 1976).…”

Modulation of the Eosinophil Chemotactic Factor (ECF) Release from Various Cells and Their Subcellular Components by Phospholipids

“…It is unresolved whether the phos pholipids facilitate the interaction of the ionophore with the cell membrane or whether they supply the cells with an addi tional source of arachidonic acid which is then liberated in the course of cell activa tion. It has also been reported that phospha-tidylinositol enhances the ionophore-and antigen-induced histamine release (9).…”