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-dimcthyl-4, 5dioxo-4 H-pyrano [3, 2-c] quinolinc-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 _pM. Furthermore, the compound inhibited not only 45C _a uptakc into the mast cells but also Ca²⁺ release from thc intraccllular Ca store at a concentration of 10 _pM in both cases. By contrast. MY-1250 did not affect either histarnine release from permeabilized mast cells induced by TPA, IP3 and GTPyS or Ca²⁺ release from the endoplasmic reticulum induced by IP3. In the chopped lung preparations, MY-1250 at doses of 10 and 100 _pM caused a significant inhibition in histarnine release from thc pieces of actively scnsitizcd 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 a-chymotrypsin activity and phospholipasc A2 activity. Also, no antagonistic effects on LTD4 and PAF were observed.