1992
DOI: 10.1161/01.hyp.19.3.281
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Inhibition by converting enzyme inhibitors of pig kidney aminopeptidase P.

Abstract: Several inhibitors of angiotensin converting enzyme were also found to inhibit aminopeptidase P, whereas inhibitors of other mammalian aminopeptidases were ineffective. Aminopeptidase P purified from pig kidney cortex was found to contain one atom of zinc per polypeptide chain, confirming its metalloenzyme nature. The concentrations of converting enzyme inhibitors required to cause 50% inhibition (I 50 ) of aminopeptidase P were in the low micromolar range. The most potent converting enzyme inhibitors toward a… Show more

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Cited by 64 publications
(54 citation statements)
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“…[1], have confirmed the earlier observations by several groups that AP-P is a metalloenzyme [3,7,12] containing 1 mol of zinc per mol of protein [13].…”
Section: Introductionsupporting
confidence: 83%
“…[1], have confirmed the earlier observations by several groups that AP-P is a metalloenzyme [3,7,12] containing 1 mol of zinc per mol of protein [13].…”
Section: Introductionsupporting
confidence: 83%
“…E. coli prolidase was reported as a Co(II) enzyme (55), while human prolidase is believed to be a Mn(II) enzyme (56). Although E. coli aminopeptidase P (57, 58) and human cytosolic homolog (59) were characterized as Mn(II) enzymes, both human and porcine membrane-bound aminopeptidase P were described as Zn(II)-containing enzymes (60,61). Several bacterial nitrile hydratases have been characterized, and they contain either cobalt or ferric ions, although they have similar sequences and share the same metal ligand residues (45,62).…”
Section: Discussionmentioning
confidence: 99%
“…With respect to the first proposal, some ACE inhibitors have been shown to inhibit aminopeptidase P, 51 which metabolizes both BK-(l-7) and BK-(l-9). Whether perindopril inhibits aminopeptidase P has not been reported, but lisinopril does not inhibit this enzyme.…”
Section: Discussionmentioning
confidence: 99%
“…Whether perindopril inhibits aminopeptidase P has not been reported, but lisinopril does not inhibit this enzyme. 51 Our demonstration that lisinopril also increased aortic levels of BK-(l-7) and BK-(l-9) at doses below the threshold for ACE inhibition shows that this action of ACE inhibitors was independent of inhibition of both "classic" ACE and aminopeptidase P. Other possible alternate pathways of BK-(l-7) and BK-(l-9) metabolism that may be inhibited by ACE inhibitors include enzymes that are related to or are isomers of ACE 52 -53 or that may be related to endopeptidase 24.15, 54 which cleaves BK-(l-9) between residues 5 and 6. 55 If such an alternate pathway exists, the present data suggest that it makes an important contribution to BK-(l-7) and BK-(1-9) metabolism in the vasculature and that vascular BK-(l-9) may play an important role in mediating some of the effects of ACE inhibitors.…”
Section: Discussionmentioning
confidence: 99%