Receptor-mediated induction of aminopeptidase A (APA) of human glomerular epithelial cells (HGEC) by glucocorticoids

FEBS Lett. 1991 Dec 9;294(3):171-4. doi: 10.1016/0014-5793(91)80661-l.

Abstract

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.

MeSH terms

  • Aldosterone / pharmacology
  • Aminopeptidases / antagonists & inhibitors
  • Aminopeptidases / biosynthesis*
  • Angiotensin II / metabolism
  • Anti-Bacterial Agents*
  • Calcium / pharmacology
  • Cycloheximide / pharmacology
  • Dactinomycin / pharmacology
  • Dexamethasone / pharmacology
  • Enzyme Induction / drug effects
  • Epithelium / enzymology
  • Glucocorticoids / pharmacology*
  • Glutamyl Aminopeptidase
  • Humans
  • Kidney Glomerulus / enzymology*
  • Mifepristone / pharmacology
  • Oligopeptides / pharmacology
  • Peptides*
  • Receptors, Glucocorticoid / physiology*

Substances

  • Anti-Bacterial Agents
  • Glucocorticoids
  • Oligopeptides
  • Peptides
  • Receptors, Glucocorticoid
  • Angiotensin II
  • Dactinomycin
  • Mifepristone
  • Aldosterone
  • amastatin
  • Dexamethasone
  • Cycloheximide
  • Aminopeptidases
  • Glutamyl Aminopeptidase
  • Calcium