Ultrastructural localization of angiotensin I-converting enzyme (EC 3.4.15.1) and neutral metalloendopeptidase (EC 3.4.24.11) in the proximal tubule of the human kidney.
We investigated the location and relative concentration in the human kidney of two enzymes involved in the processing of regulatory peptides, i.e., the angiotensin I-converting enzyme (ACE) and the neutral metalloendopeptidase 24.11 (NEP). Antibodies raised against these purified human kidney enzymes were used to determine their ultrastructural distribution by the immunogold procedure. Immunocytochemistry was performed on ultrathin frozen sections of fixed human kidney. Both enzymes were localized on the outside of the brush-border plasma membrane and, to a lesser extent, in vesicular organelles in the apical regions of epithelial cells in the proximal tubules. In addition, moderate amounts of NEP and some ACE were detected on the basal infoldings. No NEP or ACE was found in the distal tubules. Gold particles on the brush-border of proximal tubular epithelial cells were quantified with a computer based morphometry system. The results indicated about equal numbers of accessible antigenic sites for NEP and ACE on the brush-border at concentrations of antisera which yielded optimal labeling. The prominent localization of ACE and NEP on the brush-border membranes of proximal tubular epithelium suggests that these enzymes in the proximal tubules are involved in the cleavage of plasma-derived peptides after glomerular filtration.
Schulz
W W
WW
Department of Pathology, University of Texas Southwestern Medical Center, Dallas.
Hagler
H K
HK
Buja
L M
LM
Erdös
E G
EG
D000328:Adult; D005260:Female; D005629:Frozen Sections; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000201:enzymology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008871:Microvilli / Q000201:enzymology; D015260:Neprilysin / Q000032:analysis*; D007703:Peptidyl-Dipeptidase A / Q000032:analysis*
D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin