Endothelin signaling in rat thick ascending limbs. Arrows indicate stimulation, and T-lines indicate inhibition. Phosphoinositol-dependent kinase (PDK) is known to be an intermediary in other systems but has not been directly demonstrated in mediating the effects of endothelin in thick ascending limbs and so is in gray. Akt, protein kinase B; ET-1, endothelin 1; ETB, endothelin type B receptor; NKCC2, Na+-K+-2Cl− cotransporter type 2; NO, nitric oxide; NOS3, NO synthase type 3; PI3K, phosphatidylinositol 3-kinase; PIP2, phosphatidylinositol (4,5)-bisphosphate; PIP3, phosphatidylinositol (3,4,5)-trisphosphate.