Effect of an active metabolite of the antiallergic agent tazanolast on histamine release from rat mast cells

Arzneimittelforschung. 1997 Apr;47(4):390-4.

Abstract

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.

MeSH terms

  • Animals
  • Anti-Allergic Agents / pharmacology*
  • Calcium Radioisotopes
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Histamine Release / drug effects*
  • In Vitro Techniques
  • Inosine Triphosphate / metabolism
  • Male
  • Mast Cells / drug effects
  • Mast Cells / metabolism*
  • Oxalates
  • Protein Kinase C / metabolism
  • Rats
  • Rats, Wistar
  • Tetrazoles / pharmacology*
  • Type C Phospholipases / metabolism

Substances

  • Anti-Allergic Agents
  • Calcium Radioisotopes
  • Oxalates
  • Tetrazoles
  • Inosine Triphosphate
  • acitazanolast
  • Cyclic AMP
  • Protein Kinase C
  • Type C Phospholipases
  • tazanolast