Effects of nonsteroidal anti-inflammatory drugs on rat gastric mucosal phosphodiesterase activity.
In the present study, the effects of acetylsalicylic acid, diclofenac, ibuprofen, indomethacin, naproxen, phenylbutazone, proquazone, fluproquazone (RF 46-790 N), sulindac (sulfoxide and sulfide forms) and tolfenamic acid were compared on rat gastric mucosal cyclic nucleotide phosphodiesterases (PDEs). Some of the drugs inhibited PDEs effectively, the Ki values being clearly lower than those of theophylline. Mostly the type of inhibition was apparently competitive. Acetylsalicylic acid and ibuprofen were ineffective. No unambiguous correlation between the inhibition of mucosal PDEs and clinically observed gastric irritation was found. However, the inhibition of PDEs may modulate gastric side-effects of NSAIDs.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D013806:Theophylline; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases