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 (ANP R-A and ANPR-C, respectively). Exposure of mesangial cells, grown in 2 0% fetal calf serum, to 0.1% serum for 24 h increased total ANP recept or density more than 2-fold (B(max) = 87 versus 37 fmol/mg of cell pro tein) without changing binding affinity (K(d) = 94 versus 88 pM). Radi oligand binding and cross-linking studies demonstrated that up-regulat ion of ANP binding after serum deprivation was entirely due to an incr ease in ANPR-C, with little or no change in ANPR-A. Inhibition of prot ein synthesis with cycloheximide blocked up-regulation after serum dep rivation. Steady-state ANPR-C mRNA level was increased 15-fold by seru m deprivation, as judged by Northern blotting. There was no change in ANPR-A mRNA. Platelet-derived growth factor and phorbol myristate acet ate, when added to low serum medium, blocked or reversed the effect of serum deprivation on ANPR-C. We conclude that synthesis and expressio n of ANPR-C but not ANPR-A is suppressed by serum, platelet-derived gr owth factor, and phorbol myristate acetate. Suppression of ANPR-C in v ivo could contribute to mesangial cell proliferative responses to grow th factors.