[Inhibitory effect of a thromboxane A2 receptor antagonist, AA-2414, on active oxygen production by alveolar macrophages and polymorphonuclear leukocytes in guinea pigs].
We examined the effect of a thromboxane A2 receptor antagonist, AA-2414, on active oxygen production by guinea pig alveolar macrophages and peritoneal polymorphonuclear leukocytes and the xanthine-xanthine oxidase (X-XOD) system. The production of active oxygen was detected by luminol-dependent chemiluminescence (CL). AA-2414 inhibited CL of alveolar macrophages induced by zymosan, platelet activating factor (PAF) and phorbol myristate acetate (PMA) with IC50 values of 25, 8.8 and 5.6 microMs, respectively. In addition, AA-2414 reduced CL of polymorphonuclear leukocytes induced by PMA (IC50: 15 microMs). On the other hand, AA-2414 had no inhibitory effect on CL in the X-XOD system. Superoxide dismutase (SOD) reduced CL in all three of these systems. These results suggest that the active oxygen species involved in these systems is mainly the superoxide anion (O2-) and that the inhibitory action of AA-2414 on CL in guinea pig leukocytes is dependent on inhibiting the production of O2- in guinea pig leukocytes.
Matsumoto
T
T
Pharmaceutical Research Laboratories I, Takeda Chemical Industries, Ltd., Japan.
Ashida
Y
Y
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D006168:Guinea Pigs; D006538:Heptanoic Acids / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013928:Thromboxane A2 / Q000378:metabolism*
D016227:Benzoquinones; D006538:Heptanoic Acids; D017382:Reactive Oxygen Species; D017482:Receptors, Thromboxane; C060230:seratrodast; D013928:Thromboxane A2