Inhibition of rat and human prolidases by captopril.
We examined the effects of captopril on prolidase activity of crude homogenates of various tissues in the rat and in the human. It was found that captopril caused significant inhibition of prolidases from liver, kidney, and intestine in both species, whereas it showed minimal inhibitory effect on erythrocyte prolidase. In the rat, Ki for the inhibition of kidney and liver prolidases was in the range of 25-35 microM while, in the human, the value was considerably higher. The nature of inhibition was found to be competitive both in the rat and in the human. Oral administration of captopril (daily dose, 40 mg/kg) for 7 days in the rat resulted in increased urinary excretion of peptide-bound 4-hydroxy-L-proline compared to controls, indicating in vivo inhibition of tissue prolidases by captopril.
D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D004150:Dipeptidases / Q000037:antagonists & inhibitors* / Q000097:blood; D004151:Dipeptides; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D006801:Humans; D006901:Hydroxylysine / Q000652:urine; D006909:Hydroxyproline / Q000652:urine; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D013053:Spectrophotometry
D002250:Carbon Radioisotopes; D004151:Dipeptides; D006901:Hydroxylysine; C015248:glycylproline; D011392:Proline; D002216:Captopril; D004150:Dipeptidases; C022449:proline dipeptidase; D006909:Hydroxyproline