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

• Published in: Biological & pharmaceutical bulletin 1994/03/15, Vol.17(3), pp.383-385
• Main Authors: KUROKAWA, Tomofumi, MATSUMOTO, Tatsumi, ASHIDA, Yasuko, SASADA, Reiko, IWASA, Susumu
• Format: Article
• Language: English
• Subjects: (±)-7-(3, 5, 6-trimethyl-1, 4-benzoquinon-2-yl)-7-phenylheptanoic acid; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; AA-2414; Animals; anti-asthmatic agent; Asthma - drug therapy; Benzoquinones - pharmacology; Binding, Competitive - drug effects; Biological and medical sciences; CHO Cells; Cloning, Molecular; Cricetinae; Guinea Pigs; Heptanoic Acids - pharmacology; Humans; In Vitro Techniques; Medical sciences; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Pharmacology. Drug treatments; Plasmids; Prostaglandin Endoperoxides, Synthetic - pharmacokinetics; Receptors, Thromboxane - antagonists & inhibitors; Receptors, Thromboxane - biosynthesis; Receptors, Thromboxane - genetics; Respiratory system; Thromboxane A2 - analogs & derivatives; Thromboxane A2 - pharmacokinetics; thromboxane A2 receptor antagonist; Trachea - drug effects
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.17.383

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.