Inhibition by Adrenomedullin Activated Mitogen-Activated Glomerular Mesangial Cells of Arginine Vasopressin- Protein Kinase in Rat via cAMP Production

activated MAP kinase in a dose-dependent manner. When cells were preincubated for 15 min with adrenomedullin at concentrations of 1 X 10-g M or higher, the AVP-activated MAP kinase was significantly reduced. In addition, the activation of MAP kinase by phorbol-12-myristate-13-acetate (PMA) was significantly inhibited by adrenomedullin. Similarly, forskolin also diminished the activation of MAP kinase by AVP and PMA. The inhibition by adrenomedullin or forskolin of AVP-activated MAP kinase disappeared when cells were preexposed to H-89, an inhibitor of protein kinase A. These results indicate that adrenomedullin inhibits the AVP activation of MAP kinase mediated through cAMP in glomerular mesangial cells and that the site of action of adrenomedullin is behind the site of activation of protein kinase C. (Hypertens Res 1996; 19: 113-119)