Fig. 10

Proposed model of CDCA-induced cellular responses in pancreatic duct cells. CDCA acting on the plasma cell membrane induces ATP release via non-vesicular releasing mechanisms (pannexin, connexin, P2X7R, other ion channels) and vesicular exocytosis of ATP. Released ATP may in turn activate P2X receptors/cation channels and P2Y receptors, which allow Ca²⁺ influx directly (P2XR) or via G-protein coupled signalling mediate Ca²⁺ release from intracellular stores and Ca²⁺ influx (P2YR). Furthermore, CDCA may activate TGR5 receptor, which leads to stimulation of adenylyl cyclase and cAMP production, possibly increase in Ca²⁺ in some cells by yet undefined mechanisms. The sodium-calcium exchanger (NCX) can be stimulated by TGR5 resulting of transport of Ca²⁺ out of the cell, or into the cell, depending on prevailing electrochemical gradients