Functional endothelin 1 receptors on human glomerular podocytes and mesangial cells

To determine if endothelin 1 (Etl) receptors are present in human glomeruli, and which glomerular cells possess these receptors, 125I Etl binding to isolated glomeruli and cultured glomerular mesangial and epithelial cells was studied. The latter were identified as podocytes. We demonstrated that Etl binds specifically and reversibly to isolated human glomeruli and to cultured glomerular mesangial and epithelial cells. Scatchard analysis of competitive inhibition of 125I Etl binding gave the following results (m±SEM, n = 3): isolated glomeruli, Kd = 4.2± 2.1 × 10−10 M, Bmax = 8.1±1.2× 1O−10 sites/mg protein; mesangial cells, Kd = 5.2± 1.5 × 10−10 M, Bmax =1.87±0.49× 10−4 sites/cell; epithelial cells, Kd = 7.2±1.5×l0−10 M, Bmax = 2.46±0.15 × 10−4 sites/cell. These receptors seem to be functional, since in both mesangial and epithelial cells Etl induces a rapid and transient increase in intracellular [Ca2+] i . All these results indicate that Etl may regulate glomerular filtration rate through an autocrine-paracrine pathway on mesangial cells and on podocytes.