Antagonism of the Human Thromboxane A₂ Receptor by an Anti-asthmatic Agent AA-2414

Abstract

The human thromboxane A₂ receptor (TXA₂-R)-coding gene was introduced into Chinese hamster ovary cells and a cell line (TCHO-25) stably expressing TXA₂-R, at a level of 3×10⁵/cell, was obtained. An anti-asthmatic agent AA-2414 [(±)-7-(3, 5, 6-trimethyl-1, 4-benzoquinon-2-yl)-7-phenylheptanoic acid] competitively inhibited the specific binding of a TXA₂ mimic ([³H] U-46619) to the TCHO-25 cells, with an IC₅₀ of 6.0×10^-8M, indicating that the drug is an antagonist of human TXA₂-R. The TCHO-25 cells offer a tool for the screening and characterization of human TXA₂-R antagonists.