ET (sub B) receptor activation leads to activation and phosphorylation of NHE3

A study was conducted to determine whether endothelin-1 (ET-1)-induced Na+/H+ antiporter activation is related with Na+/H+ exchanger isoform 3 (NHE3) activation and phosphorylation. Results suggest that ET-1 activates NHE3. Binding of ET-1 to ET (sub B) receptors results in a two- to three-fold elevation in NHE3 phosphorylation with a dose and time dependence that parallels that of the change in activity. Serine and threonine residues are involved in phosphorylation at multiple sites.