Angiotensin II-producing enzyme III from acidified serum of nephrectomized dogs.
A highly active angiotensin-producing enzyme (enzyme III) was obtained from the serum of bilaterally nephrectomized dogs by acid treatment and ammonium sulfate fractionation. An inactive precursor (proenzyme III) was converted to enzyme III during prolonged storage (or by treatment with acid or with cathepsin G or by incubation at 38 degrees C as described in the following paper). Enzyme III reacted maximally at pH 7.7 and it produced up to 400 ng of angiotensin II/mL serum/h (i.e., amounts 4000 times higher than that generated by the endogenous renin present in serum after bilateral nephrectomy). Enzyme III produced angiotensin II at identical rates when either dog angiotensinogen or angiotensin I was used as substrate, but the rate was 710 times higher with synthetic tetradecapeptide renin substrate. Enzyme III is not identical to renin, cathepsin G, tonin, enzyme I, enzyme II, the calcium-dependent angiotensin I-converting enzyme, or the calcium-independent carboxy peptidase, which acts by sequential cleavage of angiotensin I. Enzyme III was inhibited by alpha-1-antitrypsin, diisopropyl fluorophosphate, and lima bean trypsin inhibitor (hence it is a serine proteinase). It was not inhibited by Captopril, Teprotide, or Enalapril. It had been reported previously that cathepsin G released from neutrophil granulocytes, by producing high local concentrations of angiotensin II, may provide a mobile means for modulating blood flow in tissue microvasculature during the inflammatory response. The present study offers a new, additional pathway, by enzyme III, for a similar rapid formation of angiotensin II from serum protein substrate or angiotensin I.
Haas
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E
Louis D. Beaumont Memorial Research Laboratories, Mount Sinai Medical Center, Cleveland, Ohio 44106.
Lewis
L
L
Koshy
T J
TJ
Varde
A U
AU
Renerts
L
L
Bagai
R C
RC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000096:biosynthesis*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D056649:Cathepsin G; D002403:Cathepsins / Q000494:pharmacology; D004285:Dogs; D004792:Enzyme Precursors / Q000097:blood*; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D008297:Male; D009392:Nephrectomy; D009638:Norepinephrine / Q000378:metabolism; D012697:Serine Endopeptidases / Q000097:blood* / Q000302:isolation & purification; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004792:Enzyme Precursors; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D000804:Angiotensin II; D000803:Angiotensin I; D002403:Cathepsins; D012697:Serine Endopeptidases; C061710:angiotensin II-producing serum enzyme III; D056649:Cathepsin G; D009638:Norepinephrine; D004837:Epinephrine