The relationship between energy metabolism and the action of inhibitors of histamine release

Abstract

1 Dextran-induced release of histamine from rat mast cells was inhibited equally in complete and glucose-free Tyrode solution by doxantrazole (0.03-3 micronmol/l), theophylline (0.1-3 mmol/l) and dicumarol (0.01-10 micronmol/litre). 2 Doxantrazole (3 micronmol/l), theophylline (3 mmol/l) and dicumarol (10 micronmol/l) did not reduce the adenosine 5'-triphosphate (ATP) content of mast cells in glucose-free medium. Higher concentrations of dicumarol (56-100 micronmol/l) markedly reduced the cellular ATP content. This reduction was reversed by glucose. 3 Papaverine was a more potent inhibitor of histamine release from mast cells incubated in glucose-free solution than in complete Tyrode solution (dose-ratio = 20). Like antimycin A (L MICRONMOL/L), PAPAVERINE (3 MICRONMOL/L) CAUSED A DEPLETION OF MAST CELL ATP that was greater in the absence (85%) than in the presence (25%) of extracellular glucose. 4 These results suggest that dicumarol, like doxantrazole and theophylline, inhibits histamine release without affecting mast cell energy metabolism. In contrast, papaverine probably inhibits release by depleting ATP that is required for exocytosis. 5 Inhibition of histamine release by dibutyryl cyclic adenosine 3,5'-monophosphate (1-3 mmol/l) was significantly greater when cells were incubated in complete rather than in glucose-free medium.