EVIDENCE FOR A ROLE OF PHOSPHATIDYLINOSITOL TURNOVER IN STIMULUS-SECRETION COUPLING - STUDIES WITH RAT PERITONEAL MAST-CELLS

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 [32P]P(i) and of [3H]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 Ca2+, 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 Ca2+, the secretion of histamine was either enhanced or dependent on extracellular Ca2+ (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 1 hr although histamine secretion (elicited with concanavalin A) stopped within 2 min. These results support the proposition that metabolic events involving phosphatidylinositol play a necessary intermediate role in the regulation of Ca2+ channels by ligand-activated receptors.