Inhibition of rabbit lung angiotensin converting enzyme by idrapril.
Idrapril, the prototype of a new class of angiotensin converting enzyme (ACE) inhibitors, competitively inhibited, with nanomolar apparent Ki, the hydrolysis of hippuryl-glycyl-glycine by rabbit lung ACE. The pre-steady-state analysis of this tight-binding inhibition showed it to be characterized by slow kinetics, but at variance with what was found for enalaprilat in the same conditions, idrapril appeared to act through a simple, single step mechanism. Kinetic Ki and k(on) and k(off) values were 470 pM, 3.0 +/- 1.5 x 10(6) M-1 sec-1 and 1.4 +/- 0.3 x 10(-3) sec-1, respectively.
Department of Pharmacology, Laboratori Guidotti SpA, Pisa, Italy.
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Lippi
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Criscuoli
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Sardelli
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Subissi
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015773:Enalaprilat / Q000494:pharmacology; D006898:Hydroxylamines / Q000494:pharmacology*; D007700:Kinetics; D017706:Lisinopril; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000302:isolation & purification; D011817:Rabbits
D000806:Angiotensin-Converting Enzyme Inhibitors; D003509:Cyclohexanecarboxylic Acids; D004151:Dipeptides; D006898:Hydroxylamines; C076966:idrapril; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat