Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cortex of rat kidney was homogenized and fractions enriched in plasma membrane, endoplasmic reticulum or brush border were prepared by several techniques of differential centrifugation. The identity and homogeneity of the membrane fragments were investigated by assaying marker enzymes and by transmission and scanning electron microscopy. Kallikrein was present in both plasma-membrane- and endoplasmic-reticulum-enriched fractions isolated by two fractionation procedures. Kallikrein was highly concentrated in a plasma-membrane fraction but was absent from the brush-border membrane of proximal tubular cells. Cells of transplanted renal tumours of the rat, originating from the proximal tubule, had no kallikrein activity. Kininase activity, angiotensin I-converting enzyme (kininase II) and angiotensinase were found in a plasma-membrane-enriched fraction and especially in the fraction containing isolated brush border. It is suggested that after renal kallikrein is synthesized on endoplasmic reticulum, it is subsequently reoriented to a surface membrane for activation and release. Renal kallikrein may enter the tubular filtrate distal to the proximal tubules. The brush-border membrane of proximal tubule is the major site of inactivation of kinins and angiotensin II..
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PMID:Isolation of membrane-bound renal enzymes that metabolize kinins and angiotensins. 18 28

Cultured endothelial cells provide a model for the study of interactions of vasoactive peptides with endothelium. Endothelial cell cultured from veins of human umbilical cords contain both angiotensin I converting enzyme (kininase II) and angiotensinase activities. Intact monolayers of cells can both activate angiotensin I and inactivate bradykinin when the peptides are added to culture flasks in protein-free medium. Intact suspended cells or lysed cells convert angiotensin I to angiotensin II, inactivate bradykinin, and hydrolyze hippuryldiglycine to hippuric acid and diglycine. These actions are inhibited by SQ 20881, the specific inhibitor of converting enzyme. The kininase activity of endothelial cells was partially inhibited by antibody to human lung converting enzyme. Endothelial cells also inactivate longer analogs of bradykinin, such as kallidin, methionyl-lysyl bradykinin, and bradykinin coupled covalently to 500,000 mol wt dextran. The endothelial cells retained converting enzyme activity through four successive subcultures, indicating that the enzyme is synthesized by the cells surface, and it is apparently a marker for endothelial cells, since cultured human fibroblasts, smooth muscle cells, and baby hamster kidney cells do not have it. Endothelial cells also contain an aminopheptidase which hydrolyzes both angiotensin II and the synthetic substrate, alpha-L-aspartyl beta-naphthylamide. The angiotensinase activity increased when the cells were lysed, which suggests that the enzyme is localized within the cells, Hydrolysis of both alpha-L-aspartyl beta-naphthylamide and angiotensin II was inhibited by omicron-phenanthroline, indicating that the enzyme is an A-tipe anigotensinase.
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PMID:Metabolism of vasoactive peptides by human endothelial cells in culture. Angiotensin I converting enzyme (kininase II) and angiotensinase. 19 71

1. Fractions highly enriched in plasma membrane, endoplasmic reticulum or brush border were prepared from rat kidney cortex. Kallikrein was concentrated in the plasma membrane fraction, but not in the brush border fraction. Angiotensin I-converting enzyme (kininase II) and angiotensinase were localized in the brush border membrane. 2. It is suggested that kallikrein in the urine may originate from plasma membrane distal to the brush border of proximal tubules and the conversion of angiotensin I and the inactivation of bradykinin and angiotensin II may occur on the lumen membrane of the proximal tubular cells.
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PMID:Isolation of renal membranes that contain kallikrein, angiotensin I-converting enzyme (kininase II) and angiotensinase in the rat. 19 12

By means of high voltage electrophoresis experiments it could be demonstrated that the dipeptide hydrolase present in the plasma of Bothrops jararaca is similar to the angiotensin I converting enzyme of human plasma. Therefore, angiotensin I can be considered as a probable natural substrate for this potent snake peptidase in contrast to bradykinin, which is excluded in that case, since this snake plasma was previously found to be deficient in intrinsic kinin releasing system. On the other hand, the presence of angiotensinase activity in this snake plasma could also be demonstrated. Through the pharmacological comparison of angiotensin II with the pressor peptide released from the Bothrops jararaca plasma by chymotrypsin, an indirect indication of the presence of angiotensinogen in the plasma of this reptile was obtained.
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PMID:Components of the renin-angiotensin system in the plasma of Bothrops jararaca. 20 19

In the present study, the synthesis and degradation of several potent vasoactive substances influencing coronary resistance were characterized in the isolated perfused rabbit heart. Prostaglandin synthetase activity, angiotensin converting enzyme activity, and bradykininase activity (without angiotensinase) were observed. A prostaglandin E2-like substance appeared to be the ednogenous mediator of the coronary vasodilation produced by bradykinin and angiotensin II (AII). (1) The concentration of this prostaglandinlike substance in the coronary venous effluent was directly proportional to the concentration of the coronary vasocilator stimulus (bradykinin or AII). (2) The prostaglandinlike substance released and the coronary dilation produced by the agonists correlated temporally and quantitatively. (3). Abolition of cardiac biosynthesis of the prostaglandinlike substance by indomethacin also abolished the decrease in coronary resistance produced by the agonists. AII, the most potent naturally occurring vasoconstrictor substance, produced a paradoxical coronary vasodilation because it stimulated cardiac prostaglandin biosynthesis, but the direct coronary vasoconstrictor action of AII could be readily unmasked by indomethacin, which blocks prostaglandin synthesis. The nonapeptide SQ-20881 blocked cardiac biosynthesis of AII (from angiotensin I) and enhanced the coronary vascular effects of bradykinin by interfering with bradykininase activity. Similarly, the AII-receptor antagonist, 1-Sar-8-Ile-AII, blocked the coronary vascular effect of AII.
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PMID:Hormone interactions in the isolated rabbit heart. Synthesis and coronary vasomotor effects of prostaglandins, angiotensin, and bradykinin. 119 72

The local concentration of angiotensin II (ANG II) in the renal microenvironment is not only controlled by the generation of this peptide but also by its enzymatic degradation. Angiotensinase A (ATA; aminopeptidase A, A.C.3.4.11.7) is a major exopeptidase of the glomerulus involvement in the metabolism of ANG II. We studied the glomerular mRNA levels of ATA in a remnant kidney model 1-12 weeks after 1 1/3 nephrectomy. Functional parameters (systolic blood pressure and albuminuria) demonstrated the progression of renal disease in this model. Glomerular ATA enzyme activity significantly increased 1-5 weeks after nephrectomy and returned to control levels 12 weeks after ablation. In general, changes in steady-state mRNA expression for ATA were rather small. mRNA expression for ATA in isolated glomeruli as evaluated by northern blots was slightly increased 1 and 3 weeks after 1 1/3 nephrectomy but was suppressed 5 and 12 weeks after renal ablation compared to age-matched 2-kidney controls. Treatment of animals with the ACE inhibitor ramipril for 5 and 12 weeks partly inhibited the decrease in ATA transcripts after 1 1/3 nephrectomy and stimulated expression in 2-kidney controls whereas the ACE inhibitor decreased glomerular ATA enzyme activity in nephrectomized rats at 5 weeks. Isolated glomeruli from normal controls superfused with 10(-6) M ANG II for 60 min demonstrated no change in ATA transcripts. Our results show that ATA steady-state mRNA levels are slightly elevated early (1-3 weeks) after renal ablation, and are subsequently suppressed (5-12 weeks). ATA enzyme activity is also increased early and returned (12 weeks) to levels measured in age-matched 2-kidney controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glomerular mRNA expression of angiotensinase A after renal ablation. 859 37

Aminopeptidase A is a membrane-bound zinc metalloprotease which cleaves angiotensin II into angiotensin III. Using a new specific aminopeptidase A inhibitor, EC33, we evaluated its enzymatic activity in several microdissected brain nuclei involved in the control of cardiovascular functions and in the pituitary. We compared this distribution with that of the angiotensin I-converting enzyme which converts angiotensin I to angiotensin II. Aminopeptidase A activity was heterogenously distributed with a 150-fold difference between the lowest and the highest levels. The pituitary and the circumventricular organs were the richest source of enzyme, followed by the median eminence, the arcuate nucleus, the area postrema, the choroid plexus and the supraotic and paraventricular nuclei. We did not find any close parallel between aminopeptidase A and angiotensin I-converting enzyme distributions. We examined both enzymatic activities in brain nuclei of spontaneously hypertensive rats. Aminopeptidase A activity was higher in the spontaneously hypertensive rats than in age-matched Wistar Kyoto control rats. The difference was up to 2.5-fold in several brain nuclei involved in the blood pressure regulation; in contrast, no differences in angiotensin I-converting enzyme activity were found in the same regions. The close correspondence between the distribution of aminopeptidase A activity and angiotensin receptors and nerve terminals in the brain associated with the observation that aminopeptidase A activity was overactivated in the spontaneously hypertensive rats suggest that this enzyme may contribute, at least in part, to the regulation of cardiovascular functions by its ability to convert angiotensin II to angiotensin III.
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PMID:Aminopeptidase A: distribution in rat brain nuclei and increased activity in spontaneously hypertensive rats. 917 84