title: Characterization of atrial natriuretic factor receptors in human glomerular epithelial and mesangial cells.
abstract: To evaluate the distribution and functions of receptors of atrial natriuretic factor (ANF) in human glomeruli, we studied the binding sites of ANF-(1-28) in homogeneous populations of human glomerular epithelial cells or mesangial cells. 125I-labeled ANF bound specifically to both cell types. Equilibrium saturation binding curves suggested one group of receptor sites in mesangial cells (Kd = 99 +/- 32 pmol/l, Bmax = 15.3 +/- 3.5 fmol/mg) but multiple groups in glomerular epithelial cells. Binding was greater at 37 than at 4 degrees C in mesangial cells. The reverse was observed in glomerular epithelial cells due to marked degradation of the tracer at 37 degrees C. The fractions of undisplaceable tracer in a hypertonic acid medium after 60 min incubation were 45 and 16% at 37 degrees C for glomerular epithelial and mesangial cells, respectively. ANF-(1-28) and C-ANF-(4-23), a specific ligand of clearance receptors, similarly inhibited 125I-ANF binding to mesangial cells, whereas [Ala7-Ala23]-ANF, a linear analogue, was slightly less potent. In epithelial cells, C-ANF-(4-23) competitively inhibited 125I-ANF binding but with a lower potency than ANF, whereas linear ANF at low concentrations (10-100 pmol/l) stimulated 125I-ANF binding. In addition, linear ANF markedly inhibited the degradation of 125I-ANF in the incubation medium of epithelial and mesangial cells, whereas thiorphan, an inhibitor of enkephalinase, was inactive. ANF-(1-28) stimulated cGMP production in glomerular epithelial cells but not in mesangial cells. Both analogues were inactive in both cell types and did not modify ANF-(1-28)-dependent cGMP synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 64, Hôpital Tenon, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Chansel
authors.forename: P
authors.initials: P
authors.lastname: Pham
authors.forename: M P
authors.initials: MP
authors.lastname: Nivez
authors.forename: R
authors.initials: R
authors.lastname: Ardaillou
mesh_terms: D009320:Atrial Natriuretic Factor / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism*; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: C472955:NPPA protein, human; D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP