Angiotensin I-converting enzyme in the nephron

Hall, Elizabeth R.; Kato, Jien; Erdös, Ervin G.; Robinson, Courtland; Oshima, Genichiro

doi:10.1016/0024-3205(76)90208-3

Cited by 62 publications

(22 citation statements)

References 6 publications

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“…ACE is reported to be secreted in the collecting duct and was identified immunologically along the whole length of swine nephron. 21 Besides observing the highest concentration of ACE in the brush border of proximal tubules (data not shown), we confirmed its presence in the cytoplasm of tubular cells in rabbit CCD and found increasingly strong staining at the apical membrane toward the corticomedullary boundary (Figure 4). ACE does convert Ang I to Ang II, but it might influence other processes as well.…”

Section: Discussionsupporting

confidence: 64%

Angiotensin I Conversion to Angiotensin II Stimulates Cortical Collecting Duct Sodium Transport

et al. 2003

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Abstract-Angiotensin (Ang) II directly stimulates epithelial sodium channel activity in the rabbit cortical collecting duct.Because Ang I and converting enzyme analogues might be present in the distal nephron, this raises the possibility of intraluminal generation of Ang II. Conversion of Ang I to Ang II was monitored by Ang II-dependent changes in intracellular sodium concentration as a reflection of sodium transport across the apical membrane. This involved imaging-based fluorescence microscopy with sodium-binding benzofuran isophthalate in isolated, perfused, cortical collecting-duct segments from rabbit kidney. Principal and intercalated cells were differentiated by rhodamineconjugated peanut lectin. Control principal cell intracellular sodium concentration, during perfusion with 25 mmol/L NaCl and zero sodium in the bath plus monensin (10 Ϫ5 mol/L) averaged 5.8Ϯ0.14 mmol/L (nϭ156). The increase in intracellular sodium concentration, when luminal NaCl was increased from 25 to 150 mmol/L, was elevated by 3.5-fold in the presence of intraluminal Ang I (10 Ϫ6 mol/L). Also, the effects of Ang I on sodium transport were not significantly different from the effects of Ang II (10 Ϫ9 mol/L). Ang I was used in micromolar concentrations to ensure that there was sufficient substrate available for conversion to Ang II. Inhibition of the angiotensin-converting enzyme with captopril reduced the stimulatory effect of Ang I. These results suggest that intraluminal conversion of Ang I to Ang II can occur in the cortical collecting duct, resulting in enhanced apical sodium entry.

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Section: Discussionsupporting

confidence: 64%

Angiotensin I Conversion to Angiotensin II Stimulates Cortical Collecting Duct Sodium Transport

et al. 2003

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“…As shown before by immunohistochemistry (41,42), when antibody to ACE was used, WT-ACE was uniformly distributed on the plasma membrane of cells (Fig. 7).…”

Section: Discussionmentioning

confidence: 97%

Replacement of the Transmembrane Anchor in Angiotensin I-converting Enzyme (ACE) with a Glycosylphosphatidylinositol Tail Affects Activation of the B2 Bradykinin Receptor by ACE Inhibitors

Marcic

Deddish

Skidgel

et al. 2000

Journal of Biological Chemistry

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To investigate further the relationship of angiotensin I-converting enzyme (ACE) inhibitors to activation of the B 2 bradykinin (BK) receptor, we transfected Chinese hamster ovary cells to stably express the human receptor and either wild-type ACE (WT-ACE), an ACE construct with most of the cytosolic portion deleted (Cytdel-ACE), or ACE with a glycosylphosphatidylinositol (GPI) anchor replacing the transmembrane and cytosolic domains (GPI-ACE). BK or its ACE-resistant analogue were the agonists. All activities (arachidonic acid release and calcium mobilization) were blocked by the B 2 antagonist HOE 140. B 2 was desensitized by repeated administration of BK but resensitized to agonist by ACE inhibitors in the cells expressing both B 2 and either WT-ACE or Cyt-del-ACE. In GPI-ACE expressing cells, the B 2 receptor was still activated by the agonists, but ACE inhibitors did not resensitize. Pretreatment with filipin returned the sensitivity to inhibitors. In immunocytochemistry, GPI-ACE showed patchy, uneven distribution on the plasma membrane that was restored by filipin. Thus, ACE inhibitors were inactive as long as GPI-ACE was sequestered in cholesterol-rich membrane domains. WT-ACE and B 2 receptor in Chinese hamster ovary cells co-immunoprecipitated with antibody to receptor, suggesting an interaction on the cell membrane. ACE inhibitors augment BK effects on receptors indirectly only when enzyme and receptor molecules are sterically close, possibly forming a heterodimer.Renin was discovered over a century ago (1), and kallikrein was discovered about 25 years later (2). Many of the cascading events initiated by these proteases are integrated by angiotensin I-converting enzyme (ACE) 1 or kininase II (3) as it activates angiotensin I to angiotensin II (4) and inactivates kinins (5).Subsequently, it became obvious that inhibitors of ACE affect the metabolism of both peptides (6). The successful clinical applications of ACE inhibitors have gone far beyond controlling elevated blood pressure (7, 8), but questions remain regarding which of the beneficial effects are due to inhibiting angiotensin II activation and which are caused by blocking the enzymatic breakdown of bradykinin (BK) or kallidin. The very extensive clinical applications of ACE inhibitors, not only in treating hypertension but also in treating cardiac conditions, (e.g. congestive heart failure or after myocardial infarction), and in diabetic nephropathies (9 -11), have kept attention focused on this issue. In laboratory experiments and in some clinical studies (12, 13), many effects of ACE inhibitors were abolished by the BK B 2 receptor blocker HOE 140. Although it was assumed that these effects were due to inhibiting the inactivation of BK, early bioassays already indicated that substances that did not prolong the half-life of BK still potentiated its actions on the isolated guinea pig ileum (14). Experiments on isolated guinea pig atria demonstrated that ACE inhibitors can resensitize the heart tissue desensitized by a B 2 receptor agonist (15). ...

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“…When the converting enzyme was purified from homogenates of lung, however, a substantial amount of activity was in the soluble fraction (21). In the kidney, the converting enzyme is concentrated on the brush border of epithelial cells in the proximal tubules (5,39,40).…”

Section: Discussionmentioning

confidence: 99%

Metabolism of vasoactive peptides by human endothelial cells in culture. Angiotensin I converting enzyme (kininase II) and angiotensinase.

Johnson¹,

Erdös²

1977

J. Clin. Invest.

189

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Angiotensin I-converting enzyme in the nephron

Cited by 62 publications

References 6 publications

Angiotensin I Conversion to Angiotensin II Stimulates Cortical Collecting Duct Sodium Transport

Angiotensin I Conversion to Angiotensin II Stimulates Cortical Collecting Duct Sodium Transport

Replacement of the Transmembrane Anchor in Angiotensin I-converting Enzyme (ACE) with a Glycosylphosphatidylinositol Tail Affects Activation of the B2 Bradykinin Receptor by ACE Inhibitors

Metabolism of vasoactive peptides by human endothelial cells in culture. Angiotensin I converting enzyme (kininase II) and angiotensinase.

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