ECTOENZYMES OF PEPTIDIC METABOLISM IN REN AL GLOMERULAR AND VASCULAR CELLS

The ectoenzymes acting in the metabolism of peptides play an essential role in renal cell-cell communication. We have studied four of these ectoenzymes, aminopeptidases N and A (APN, APA), dipeptidylpeptidase I V (DPP IV) and neutral endopeptidase (NEP) in cultured human glomerula r mesangial and epithelial cells and cultured rabbit renal cortical va scular smooth muscle cells. APN is present at the surface of both mesa ngial and epithelial cells with identical characteristics. Its express ion (enzyme activity and immunoreactive protein) is induced by phorbol esters and other protein kinase C-stimulating agents. APA is present o nly in glomerular epithelial cells. Its expression is induced by gluco corticoids and cyclic AMP-stimulating agents. DPP IV is also present o nly in glomerular epithelial cells. Its expression (enzyme activity, i mmunoreactive protein and mRNA) is induced by interferon gamma. NEP is present in glomerular epithelial cells and vascular smooth muscle cel ls. The expression of the latter enzyme is inhibited in the presence o f serum via the combined effect of Ca(i)2+ and PKC-stimulating agents. In contrast, glucocorticoids and cyclic GMP induce its expression. NE P plays a major role in the catabolism by these cells of atrial natriu retic factor. All these data emphasize the multiplicity of the mechani sms controlling ectopeptidase expression in cultured glomerular and re nal vascular cells.