Fig. 3.

ET binds to ET_A receptor, stimulates PLCβ, and increases production of IP₃ and DAG. IP₃ stimulates Ca²⁺ release from the SR. ET also stimulates Ca²⁺ entry through Ca²⁺ channels. Ca²⁺ binds calmodulin (CAM), activates myosin light chain (MLC) kinase, causes MLC phosphorylation, and initiates VSM contraction. DAG activates PKC. PKC could phosphorylate calponin (CaP) and/or activate a protein kinase cascade involving Raf, MAPK kinase (MEK) and MAPK, leading to phosphorylation of caldesmon (CaD) and an increase in the myofilament force sensitivity to Ca²⁺. ET_A receptor-mediated activation of MAPK could induce gene transcription and VSM growth. ET_B2 receptors could activate similar mechanisms of VSM contraction/growth.