Mechanism of action of MY-1250, an active metabolite of Repirinast, in inhibiting histamine release from rat mast cells.
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.
Takei
M
M
Department of Pharmacology, Tokushima Bunri University, Japan.
Endo
K
K
Takahashi
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001200:Ascaris / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D006633:Histamine Antagonists / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D010529:Peritoneal Cavity / Q000166:cytology; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D015363:Quinolones; C048522:repirinast; C049488:MY 1250; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D002118:Calcium