EFFECT OF AN ACTIVE METABOLITE OF THE ANTIALLERGIC AGENT TAZANOLAST ON HISTAMINE-RELEASE FROM RAT MAST-CELLS

WP-871 (3'-(1H-tetrazol-5-yl)oxanilic acid monohydrate, CAS 114607-46- 4) is a monohydrata of a main active metabolite of tazanolast (butyl 3 '-(1H-tetrazol-5-yl) oxanilate, CAS 82989-25-1), an orally active anti allergic drug. WP-871 inhibited dose-dependently compound 48/80-induce d histamine release from rat peritoneal mast cells. In a similar dose range, WP-871 was effective in inhibiting compound 48/80-induced Ca-45 uptake into mast cells from extracellular medium and compound 48/80-i nduced translocation of protein kinase C from the cytosol to the membr ane fraction of mast cells. WP-871 also inhibited inositol trisphospha te production but did not exhibit a direct inhibitory effect on phosph olipase C in mast cells. WP-871 caused no increase in cAMP content in mast cells. These results suggest that WP-871 may inhibit histamine re lease mainly by preventing the increase in intracellular Ca2+ concentr ation, which is a critical event in signal transduction leading to his tamine release in mast cells.