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THE RELATIONSHIP BETWEEN ENERGY METABOLISM AND THE ACTION OF INHIBITORS OF HISTAMINE RELEASE
Author(s) -
GARLAND L.G.,
JOHANSEN T.
Publication year - 1977
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1977.tb08410.x
Subject(s) - histamine , theophylline , antimycin a , chemistry , papaverine , adenosine , extracellular , mast cell , adenosine triphosphate , endocrinology , metabolism , medicine , biochemistry , biology , mitochondrion , immunology
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 μmol/l), theophylline (0.1–3 mmol/l) and dicumarol (0.01–10 μmol/litre). 2 Doxantrazole (3 μmol/l), theophylline (3 mmol/l) and dicumarol (10 μmol/l) did not reduce the adenosine 5′‐triphosphate (ATP) content of mast cells in glucose‐free medium. Higher concentrations of dicumarol (56–100 μmol/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 (1 μmol/l), papaverine (3 μmol/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.