Receptor-mediated induction of aminopeptidase A (APA) of human glomerular epithelial cells (HGEC) by glucocorticoids.
Membrane-bound peptidases are critical regulators of peptide hormones. We therefore characterized aminopeptidase A (APA) activity in human glomerular epithelial cells (HGEC) and studied the control of its expression. APA, which splits off the N-terminal Asp from angiotensin II (AII), was present at the surface of HGECs (55% of the total enzyme). APA activity was calcium-dependent and was inhibited by amastatin. Treatment of HGECs by dexamethasone (DEX) increased ecto-APA activity in a dose- and time-dependent manner. Maximal increase of APA activity (x 2) occurred after treatment with 0.5 microM DEX for 5 days. HIgher concentrations (1-10 microM) of aldosterone (ALD) stimulated APA activity to a lesser extent (x 1.25). Actinomycin D and cycloheximide prevented and RU 38486, a glucocorticoid receptor antagonist, suppressed the DEX-induced increase in APA activity. These results indicate that AII availability at glomerular receptor sites may be reduced by DEX and suggest a role for glucocorticoids in AII-dependent changes of glomerular filtration rate.
Stefanovic
V
V
INSERM 64, Hôpital Tenon, Paris, France.
Vlahovic
P
P
Ardaillou
N
N
Ardaillou
R
R
D000450:Aldosterone / Q000494:pharmacology; D000626:Aminopeptidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000804:Angiotensin II / Q000378:metabolism; D000900:Anti-Bacterial Agents; D002118:Calcium / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004848:Epithelium / Q000201:enzymology; D005938:Glucocorticoids / Q000494:pharmacology*; D043384:Glutamyl Aminopeptidase; D006801:Humans; D007678:Kidney Glomerulus / Q000201:enzymology*; D015735:Mifepristone / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides; D011965:Receptors, Glucocorticoid / Q000502:physiology*
D000900:Anti-Bacterial Agents; D005938:Glucocorticoids; D009842:Oligopeptides; D010455:Peptides; D011965:Receptors, Glucocorticoid; D000804:Angiotensin II; D003609:Dactinomycin; D015735:Mifepristone; D000450:Aldosterone; C016977:amastatin; D003907:Dexamethasone; D003513:Cycloheximide; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase; D002118:Calcium