title: Inhibitory effect of MY-1250 on histamine release from rat peritoneal mast cells and guinea pig lung fragments: the elucidation of the mechanism.
abstract: When the effect of MY-1250 (5,6-dihydro-7,8-dimethyl-4,5-dioxo-4 H-pyrano [3,2-c] quinoline-2-carboxylic acid) on histamine release from rat peritoneal mast cells induced by compound 48/80 was studied, MY-1250 caused a significant inhibition of histamine release at concentrations higher than 3 microM. Furthermore, the compound inhibited not only 45C a uptake into the mast cells but also Ca2+ release from the intracellular Ca store at a concentration of 10 microM in both cases. By contrast, MY-1250 did not affect either histamine release from permeabilized mast cells induced by TPA, IP3 and GTP gamma S or Ca2+ release from the endoplasmic reticulum induced by IP3. In the chopped lung preparations, MY-1250 at doses of 10 and 100 microM caused a significant inhibition in histamine release from the pieces of actively sensitized guinea pigs exposed to antigen and simultaneously prevented a decrease in intracellular cAMP contents taking place in association with antigen-antibody reaction. No significant changes were effected by MY-1250 in alpha-chymotrypsin activity and phospholipase A2 activity. Also, no antagonistic effects on LTD4 and PAF were observed.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Kamei
authors.forename: M
authors.initials: M
authors.lastname: Mio
authors.forename: K
authors.initials: K
authors.lastname: Izushi
authors.forename: N
authors.initials: N
authors.lastname: Yoshii
authors.forename: K
authors.initials: K
authors.lastname: Fujisawa
authors.forename: K
authors.initials: K
authors.lastname: Tasaka
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000032:analysis; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D006634:Histamine H1 Antagonists; D010972:Platelet Activating Factor; D015363:Quinolones; D003189:p-Methoxy-N-methylphenethylamine; C049488:MY 1250; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D002118:Calcium