Cutting edge: agonistic effect of indomethacin on a prostaglandin D2 receptor, CRTH2.
Hirai H1,
Tanaka K,
Takano S,
Ichimasa M,
Nakamura M,
Nagata K.
Author information
Abstract
Indomethacin is a widely used nonsteroidal anti-inflammatory drug and is generally known to exhibit its multiple biological functions by inhibiting cyclooxygenases or activating peroxisome proliferator-activated receptors. In this study,
we present evidence demonstrating that the novel PGD(2) receptor chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) is another functional target for indomethacin. Indomethacin induced Ca(2+) mobilization in CRTH2-transfected K562 cells at submicromolar concentrations (approximate EC(50), 50 nM) in a G(alphai)-dependent manner as PGD(2) did. Other nonsteroidal anti-inflammatory drugs (aspirin, sulindac, diclofenac, and acemetacin) had no such effect even at micromolar concentrations.
In chemotaxis assay, three CRTH2-expressing cell types, Th2 cells, eosinophils, and basophils, were all significantly attracted by indomethacin (EC(50), 50-500 nM) as well as by PGD(2) (EC(50), 2-20 nM), and the effects of indomethacin were blocked by anti-CRTH2 mAb. These results
suggest the involvement of CRTH2 in mediating some of therapeutic and/or unwanted side effects of indomethacin, independently of cyclooxygenases and peroxisome proliferator-activated receptors.
= Indomethacin ups CRTH2, despite inhibiting COX-2(and hence, PGD2). This means Indomethacin itself is a substrate(aka substitute in place of PGD2) for CRTH2-binding.
They stopped selling it not because the stuff was fake, but because it causes hairloss via the same mechanism as PGD2(people thought COX-2 inhibitors were good for hair because they inhibit PGD2)
