Identification of the thromboxane A2 receptor in hepatic sinusoidal endothelial cells and its role in Endotoxin-induced liver injury in rats

✍ Scribed by Satoshi Ishiguro; Shigeki Arii; Kazunobu Monden; Yukito Adachi; Naomi Funaki; Hiroaki Higashitsuji; Shin-Ichi Fujita; Masaharu Furutani; Masahiro Mise; Tadahiro Kitao; Toshio Nakamura; Fumitaka Ushikubi; Ken-Ichi Nakamura; Shuh Narumiya; Katsuhiko Enomoto; Tousei Ohmura; Michio Mori; Masayuki Imamura

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 687 KB
• Volume: 20
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840200527

✦ Synopsis

The presence of the thromboxane A, receptor in sinusoidal endothelial cells was investigated and its pathogenic role in endotoxin-induced liver injury examined. The receptor was measured with a binding assay using a specific thromboxane A, receptor antagonist, [3H]S-145. Scatchard analysis of the binding indicated the presence of a single class of high-affinity binding sites with a dissociation constant of 5.00 2 0.96 nmolb, a maximal binding of 22.85 f 2.71 fmol/lOs cells and 13.80 f 1.60 x lo3 binding sites per cell. The addition of a cyclooxygenase inhibitor, indomethacin, during the cell preparation increased the maximal binding value and the number of binding sites of 37.34 2 3.01 and 22.50 2 1.80 x lo3 sites/cell, respectively. The binding was displaced by various thromboxane A, analogs such as ONO-3708 and STA, but was not effectively competed for by other prostaglandins. Endotoxin injection reduced dissociation constant, maximal binding and the number of binding sites in sinusoidal endothelial cells to 3.49 f 0.87 nmolb, 6.03 f 0.64 fmol/106 cells and 3.65 f 0.39 x lo3 sites/cell, respectively. A cyclooxygenase inhibitor and a Kupffer cell inhibitor added before endotoxin treatment significantly prevented the reduction in the number of thromboxane A, receptors. It is possible that these effects were due to a reduction in the agonist-induced internalization of the thromboxane A, receptor brought about by the prevention of throm-