[Inhibitory effect of nafamostat mesilate (FUT-175) on O2- production in rat polymorphonuclear leucocytes].
Effect of nafamostat mesilate (FUT-175), a serine protease inhibitor, having anti-inflammatory effects was studied on superoxide (O2-) production in rat polymorphonuclear leucocytes (PMN) and compared with those of other serine protease inhibitors and typical anti-inflammatory agents. 1) O2- productions in rat PMN stimulated with concanavalin A (Con A) and cytochalasin B (Cyt B) were too weak to observe. With NADH, however, strong O2- production was induced by Con A and Cyt B. 2) FUT-175 at 10(-6) and 10(-5) M inhibited O2- production in rat PMN induced by Con A and Cyt B with NADH in a concentration-dependent manner. 3) The serine protease inhibitor L-tosylamido-2-phenylethyl-chloromethyl ketone (TPCK) and soybean trypsin inhibitor (SBTI) inhibited O2- production at 10(-5) M and 10(-4) M, respectively, while aprotinin, chymostatin and leupeptin did not. 4) Neither indomethacin nor dexamethasone, typical anti-inflammatory agents, inhibited O2- production. Mepacrine, a phospholipase A2 inhibitor, strongly inhibited it. 5) O2- production in PMN prepared from the rat administered FUT-175, 200 mg/kg, p.o., was significantly decreased in comparison with that of the control rat. 6) FUT-175 had no effect on O2- production by hypoxanthine-xanthine oxidase. These results showed FUT-175 had a strong inhibitory effect on O2- production in rat PMN which other typical anti-inflammatory agents did not have.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001550:Benzamidines; D003208:Concanavalin A / Q000037:antagonists & inhibitors; D003571:Cytochalasin B / Q000037:antagonists & inhibitors; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009243:NAD / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D001550:Benzamidines; D006146:Guanidines; D007042:Hypoxanthines; D011480:Protease Inhibitors; D009243:NAD; D003208:Concanavalin A; D013481:Superoxides; D019271:Hypoxanthine; D003571:Cytochalasin B; D014969:Xanthine Oxidase; C032855:nafamostat