Fig. 18.

Model for PGE2 action in mIMCD-K2 cells. PGE2 in the apical side of cells can be transported to the basal side through the prostaglandin transporter (PGT). Once PGE2 reaches the basolateral membrane, it can bind to EP4 receptors in an autocrine or paracrine fashion. Binding of EP4 receptor induces activation of adenylate cyclase (AC) to increase cAMP production and stimulate protein kinase A (PKA) activity. PKA can directly stimulate CFTR; additionally PKA may phosphorylate IP₃ receptors, which may sensitize them to basal levels of IP₃. This could augment IP₃ receptor response and enhance release Ca²⁺ from intracellular stores. An increase in intracellular Ca²⁺ activates Ca²⁺-activated Cl⁻ channel (CACC) and perhaps CFTR activity.