Regulation of atrial natriuretic peptide clearance receptors in mesangial cells by growth factors.
Rat mesangial cells can express both 130-kDa guanylyl cyclase-coupled and 66-kDa non-coupled atrial natriuretic peptide (ANP) receptors (ANPR-A and ANPR-C, respectively). Exposure of mesangial cells, grown in 20% fetal calf serum, to 0.1% serum for 24 h increased total ANP receptor density more than 2-fold (Bmax = 87 versus 37 fmol/mg of cell protein) without changing binding affinity (Kd = 94 versus 88 pM). Radioligand binding and cross-linking studies demonstrated that up-regulation of ANP binding after serum deprivation was entirely due to an increase in ANPR-C, with little or no change in ANPR-A. Inhibition of protein synthesis with cycloheximide blocked up-regulation after serum deprivation. Steady-state ANPR-C mRNA level was increased 15-fold by serum deprivation, as judged by Northern blotting. There was no change in ANPR-A mRNA. Platelet-derived growth factor and phorbol myristate acetate, when added to low serum medium, blocked or reversed the effect of serum deprivation on ANPR-C. We conclude that synthesis and expression of ANPR-C but not ANPR-A is suppressed by serum, platelet-derived growth factor, and phorbol myristate acetate. Suppression of ANPR-C in vivo could contribute to mesangial cell proliferative responses to growth factors.
Paul
R V
RV
Division of Nephrology, Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina.
Wackym
P S
PS
Budisavljevic
M
M
Everett
E
E
Norris
J S
JS
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D001667:Binding, Competitive; D015152:Blotting, Northern; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004261:DNA Replication / Q000187:drug effects; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D015854:Up-Regulation
D016895:Culture Media, Serum-Free; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D013936:Thymidine