Antagonism of the human thromboxane A2 receptor by an anti-asthmatic agent AA-2414

Biol Pharm Bull. 1994 Mar;17(3):383-5. doi: 10.1248/bpb.17.383.

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 x 10(5)/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 x 10(-8) M, 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.

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Animals
  • Asthma / drug therapy*
  • Benzoquinones / pharmacology*
  • Binding, Competitive / drug effects
  • CHO Cells
  • Cloning, Molecular
  • Cricetinae
  • Guinea Pigs
  • Heptanoic Acids / pharmacology*
  • Humans
  • In Vitro Techniques
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Plasmids
  • Prostaglandin Endoperoxides, Synthetic / pharmacokinetics
  • Receptors, Thromboxane / antagonists & inhibitors*
  • Receptors, Thromboxane / biosynthesis
  • Receptors, Thromboxane / genetics
  • Thromboxane A2 / analogs & derivatives
  • Thromboxane A2 / pharmacokinetics
  • Trachea / drug effects

Substances

  • Benzoquinones
  • Heptanoic Acids
  • Prostaglandin Endoperoxides, Synthetic
  • Receptors, Thromboxane
  • seratrodast
  • Thromboxane A2
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid