Endothelin-1 Stimulates Contraction of Rat Glomerular Mesangial Cells and Potentiates fl-Adrenergic-mediated Cyclic Adenosine Monophosphate Accumulation

The newly isolated peptide, endothelin-1 (ET-1), is a potent pressor agent that reduces GFR and the glomerular ultrafil-tration coefficient. Recent evidence demonstrates that ET-1 mobilizes intracellular Ca2 " (ICa2+Ii) in glomerular mesangial cells by activating the phosphoinositide cascade. The present experiments were designed to examine whether ET-1 stimu-lates mesangial cell contraction and regulates the synthesis of PGE2 and cAMP, which dampen vasoconstrictor-induced mes-angial contraction. ET-1 (2 1 nM) reduced the cross-sectional area of rat mesangial cells cultured on three-dimensional gels of collagen type I. ET-1 also caused complex rearrangements of F-actin microfilaments consistent with a motile response. Contraction in response to ET-1 occurred only at concentra-tions that activate phospholipase C, and contraction was unaf