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.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D050356:Lipid Metabolism; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013873:Thionucleotides / Q000494:pharmacology*
D001095:Arachidonic Acids; D013873:Thionucleotides; D016718:Arachidonic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate