[Effect of thromboxane A2 synthetase inhibitor (OKY-046) on leukotriene C4-induced airway hyperresponsiveness in guinea pigs].
In this study, we investigated the effects of peroral (p.o.) administration of a thromboxane A2 (TXA2) synthetase inhibitor, OKY-046, on the airway hyperresponsiveness (AHR) in guinea pigs induced by intravenous administration of leukotriene C4 (LTC4). A 3 micrograms/kg/hr LTC4 infusion induced airway wall thickening (AWT) and AHR to 1.8 and 3.6 micrograms/kg histamine bolus shot. OKY-046 100 mg/kg p.o. partially inhibited the AHR induced by LTC4 without inhibition of AWT. Previously, we have reported that LTC4-induced AHR was partially inhibited, to the same exert as by OKY-046, by TXA2 receptor antagonists, ONO-NT-126 and ONO-8809. These data suggest that intravenous administration of LTC4 generates TXA2, and TXA2 augments LTC4-induced AHR partially in guinea pigs.
Tsukagoshi
H
H
First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Yodonawa
S
S
Kurosawa
M
M
D000284:Administration, Oral; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy*; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008297:Male; D008689:Methacrylates / Q000008:administration & dosage / Q000627:therapeutic use*; D013189:SRS-A / Q000008:administration & dosage / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000502:physiology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D008689:Methacrylates; D013189:SRS-A; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; C034364:ozagrel