ATRIAL-NATRIURETIC-PEPTIDE INHIBITS ENDOTHELIN-1-INDUCED ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE IN CULTURED RAT MESANGIAL CELLS

In cultured rat glomerular mesangial cells, endothelin-1 (ET−1) activated both pp 44 and pp 42 mitogen-activated protein (MAP) kinases. Atrial natriuretic peptide (ANP) inhibited ET−1-induced activation of both pp44 and pp 42 MAP kinases. ANP also inhibited ET−1-induced translocation of protein kinase C (PKC) and TPA-induced activation of MAP kinase. These results indicate that ANP modulates the functions of mesangial cells, including proliferation and contraction through the inhibition of ET−1-induced activation of MAP kinase in various steps proximal to MAP kinase. © 1993 Academic Press, Inc.