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 monohydrate of a main active metabolite of tazanolast (butyl 3'-(1H-tetrazol-5-yl) oxanilate, CAS 82989-25-1), an orally active antiallergic drug. WP-871 inhibited dose-dependently compound 48/80-induced histamine release from rat peritoneal mast cells. In a similar dose range, WP-871 was effective in inhibiting compound 48/80-induced 45Ca uptake into mast cells from extracellular medium and compound 48/80-induced translocation of protein kinase C from the cytosol to the membrane fraction of mast cells. WP-871 also inhibited inositol trisphosphate production but did not exhibit a direct inhibitory effect on phospholipase C in mast cells. WP-871 caused no increase in cAMP content in mast cells. These results suggest that WP-871 may inhibit histamine release mainly by preventing the increase in intracellular Ca2+ concentration, which is a critical event in signal transduction leading to histamine release in mast cells.
Kamei
C
C
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama, University, Japan.
Mio
M
M
Yoshida
T
T
Saito
Y
Y
Toyoda
Y
Y
Tsuriya
Y
Y
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D007293:Inosine Triphosphate / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D010070:Oxalates; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism
D018926:Anti-Allergic Agents; D002132:Calcium Radioisotopes; D010070:Oxalates; D013777:Tetrazoles; D007293:Inosine Triphosphate; C065288:acitazanolast; D000242:Cyclic AMP; D011493:Protein Kinase C; D010738:Type C Phospholipases; C106301:tazanolast