Assessment of kininases in rheumatic diseases and the effect of therapeutic agents.
Bradykinin is degraded in human plasma by a carboxypeptidase to yield desArg9-bradykinin (DBK) which is then digested by angiotensin-converting enzyme (ACE) to the pentapeptide Arg-Pro-Pro-Gly-Phe and the tripeptide Ser-Pro-Phe. We have studied the rate of kinin degradation by each of these enzymes in patients with rheumatoid arthritis (RA) and with systemic lupus erythematosus (SLE), compared with the degradation rate in degenerative joint disease and normal subjects. Carboxypeptidase activity was the same in all individuals, but ACE activity was increased in the RA and SLE patients. We examined the effects of aspirin, sodium salicylate, auranofin, penicillamine, and corticosteroids on kinin metabolism, and all of these were marked inhibitors of ACE; however, only penicillamine had any demonstrable inhibition of carboxypeptidase. These observations suggest rapid degradation of DBK in patients with untreated RA and SLE, whereas drugs utilized in therapy have the opposite effects. Studies to examine the role of DBK in disease manifestations are in progress.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007705:Kinins / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D001121:Lysine Carboxypeptidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D010396:Penicillamine / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism*; D013256:Steroids
D000806:Angiotensin-Converting Enzyme Inhibitors; D000893:Anti-Inflammatory Agents; D007705:Kinins; D013256:Steroids; C024626:bradykinin, des-Arg(9)-; D007703:Peptidyl-Dipeptidase A; D001121:Lysine Carboxypeptidase; D010396:Penicillamine; D001920:Bradykinin