Mechanism of Action of MY-1250, an Active Metabolite of Repirinast, in Inhibiting Histamine Release from Rat Mast Cells

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1992 Mar 1

PMID 1378339

Authors

M Takei

K Endo

K Takahashi

Affiliations

Soon will be listed here.

Abstract

1. When MY-1250 (3.6 x 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 [Ca2+]i and the histamine release induced by DNP-AS antigen (40 micrograms 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-125 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 [Ca2+]i and histamine release induced by antigen was due to the inhibition of ATP-dependent Ca(2+)-release from the intracellular Ca(2+)-stores.

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