ADRENOMEDULLIN BINDS WITH HIGH-AFFINITY, ELEVATES CYCLIC-AMP, AND STIMULATES C-FOS MESSENGER-RNA IN C6 GLIOMA-CELLS

The effects of adrenomedul lin (ADM) on C6 glioma cells were investiga ted. [I-125]ADM bound with high affinity (K-d = 24 nM) to a single cla ss of sites (B-max = 36,000/cell) in C6 cells. Specific [I-125]ADM bin ding was inhibited with high affinity by ADM (IC50 value of 10 nM) but not ADM(22-52) or pro-adrenomedullin N-terminal 20 peptide (PAMP). By RT-PCR, ADM receptors were detected in C6 cells. ADM elevated cAMP (E D50 value of 10 nM) whereas PAMP and ADM(22-52) did not. ADM stimulate d transiently c-fos mRNA in a concentration-dependent manner. Monoclon al antibody G6, which neutralizes ADM, significantly inhibited C6 prol iferation and decreased the ability of ADM to elevate c-fos mRNA. Thes e data suggest that ADM is a regulatory peptide of C6 cells. (C) 1997 Elsevier Science Inc.