Antagonism of the human thromboxane A2 receptor by an anti-asthmatic agent AA-2414.
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.
DDS Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
T
T
Kurokawa
T
T
Matsumoto
Y
Y
Ashida
R
R
Sasada
S
S
Iwasa
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D016227:Benzoquinones / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D006168:Guinea Pigs; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010957:Plasmids; D011450:Prostaglandin Endoperoxides, Synthetic / Q000493:pharmacokinetics; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D014132:Trachea / Q000187:drug effects
D016227:Benzoquinones; D006538:Heptanoic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D017482:Receptors, Thromboxane; C060230:seratrodast; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid