Guanosine 5'-(gamma-thio)triphosphate stimulates arachidonic acid liberation in permeabilized rat peritoneal mast cells.

The exocytotic histamine secretion from ATP-permeabilized and Mg-resealed rat peritoneal mast cells is markedly enhanced by the addition of guanosine 5'-(gamma-thio)triphosphate (GTP gamma S) at a concentration of 100 uM. GTP gamma S also caused a great enhancement of arachidonic acid liberation from these cells. The level of released arachidonic acid in permeabilized cells enhanced by GTP gamma S in the absence of Ca2+ was nearly equal to the level of permeabilized cells incubated in the presence of Ca2+ but without GTP gamma S, suggesting the Ca2+ sparing effect of GTP gamma S. From the time sequential changes in the [3H]arachidonate radioactivities in various phospholipids, it is conceivable that nucleotide-dependent arachidonic acid release was mediated via phospholipase A2 pathway. The entrapment of a diacylglycerol (DG) lipase inhibitor, RHC 80267, caused suppression of both Ca2+- and guanine nucleotide-dependent arachidonic acid liberation in mast cells, indicating contribution of DG lipase pathway for arachidonic acid generation.