Dual effects of a basic anti-inflammatory agent, 2-aminomethyl-4-t-butyl-6-iodophenol hydrochloride (MK-447), on biosynthesis of prostaglandin endoperoxides.
Effects of MK-447 on prostaglandin (PG) endoperoxide formation from arachidonic acid by bovine seminal vesicle microsomes in the presence of cofactors (hemoglobin and tryptophan) were studied by cascade superfusion on rabbit aorta and mesenteric artery and rat stomach and colon. In the presence of hemoglobin (0.2 muM), MK-447 (up to 30 muM) accelerated PG endoperoxide formation, as tryptophan did, whereas higher concentrations of MK-447 lost the acceleration effect and finally inhibited the PG endoperoxide formation. Increased concentration of hemoglobin (2 muM) shifted the dose of MK-447 for peak generation from 30 to 100 muM. Thus, MK-447 shows dual action, acceleration and inhibition, on the PG endoperoxide formation.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives* / Q000494:pharmacology; D002417:Cattle; D004357:Drug Synergism; D006454:Hemoglobins / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000378:metabolism; D011449:Prostaglandin Endoperoxides / Q000096:biosynthesis*; D011817:Rabbits; D051381:Rats; D012669:Seminal Vesicles / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D006454:Hemoglobins; D011449:Prostaglandin Endoperoxides; D002084:Butylated Hydroxytoluene; C013753:2-aminomethyl-4-t-butyl-6-iodophenol; D014364:Tryptophan