On the mode of action and biochemical properties of anti-inflammatory drugs-II.
The inhibition of prostaglandin (PG) synthetase by nonsteroidal anti-inflammatory drugs (NSAID) is not well understood. Co-factors (glutathione and hydroquinone) are needed for maximum enzymatic activity in vitro, and we suggest that NSAID might inhibit PG synthetase partly by interfering with co-factor induced stimulation of the enzyme. This hypothesis was tested by: A) Examining the effect of glutathione, noradrenaline and hydroquinone on bull seminal vesicle (BSV) PG synthetase in vitro. The stimulatory effects were concentration-dependent. B) Three structurally distinct NSAID, indomethacin, aspirin and paracetamol, inhibited the stimulation by each co-factor in a concentration-related manner. Drug effectiveness also depended on the concentration of co-factor.
D000082:Acetaminophen / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D002417:Cattle; D005978:Glutathione / Q000494:pharmacology; D006873:Hydroquinones / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012669:Seminal Vesicles / Q000187:drug effects / Q000201:enzymology*
D000893:Anti-Inflammatory Agents; D006873:Hydroquinones; D000082:Acetaminophen; D006899:Mixed Function Oxygenases; D011451:Prostaglandin-Endoperoxide Synthases; D005978:Glutathione; D001241:Aspirin; D009638:Norepinephrine; D007213:Indomethacin