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Mechanism of action of MY‐1250, an active metabolite of Repirinast, in inhibiting histamine release from rat mast cells
Author(s) -
Takei Masao,
Endo Koichi,
Takahashi Kazuo
Publication year - 1992
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.1476-5381.1992.tb09023.x
Subject(s) - histamine , adenosine , intracellular , chemistry , calcium , mechanism of action , metabolite , adenosine triphosphate , incubation , adenosine monophosphate , mast cell , inhibitory postsynaptic potential , medicine , endocrinology , biochemistry , biology , immunology , in vitro , organic chemistry
1 When MY‐1250 (3.6 × 10 −5 m ) was added to mast cells, it caused a rapid increase in adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) and decrease in adenosine 5′‐triphosphate (ATP), both of which recovered to their original levels within 2 min. The accumulation of cyclic AMP was maximal at 20 s after challenge with MY‐1250. The minimum level of ATP was observed at 20 s after addition of MY‐1250. 2 The initial rise in [Ca 2+ ] i and the histamine release induced by DNP‐AS antigen (40 μg ml −1 ) was most strongly inhibited at 20 s after incubation of the mast cells with MY‐1250. 3 MY‐1250 strongly and dose‐dependently inhibited the histamine release from rat mast cells induced by antigen. Moreover, MY‐1250 strongly inhibited calcium ion mobilization from the intracellular Ca 2+ ‐store. 4 These results suggested that the inhibitory mechanism of MY‐1250 on the initial rise in [Ca 2+ ] i and histamine release induced by antigen was due to the inhibition of ATP‐dependent Ca 2+ ‐release from the intracellular Ca 2+ ‐stores.