PC-1 and PC-2 allows primary cilia to function as a mechanosensor. The bending of cholangiocytes primary cilia by luminal flow induces an increase in the intracellular ionic calcium through activation of PC-1 and PC-2, leading to inhibition of AC6, which is inhibited by calcium, resulting in a decrease in levels of cAMP and inhibition of PKA. TRPV4 participates in the osmosensory activity. This receptor is activated by extracellular hypotonicity and inhibited by extracellular hypertonicity, leading to an increase in intracellular calcium that results in PKA inhibition. The cilia chemosensory response is a consequence of purinergic receptors (P2Y12) and bile acid receptor (TGR5), which are activated causing changes in intracellular cAMP levels, possibly via AC6, that induces PKA activation or inhibition. PC-1: polycystin-1; PC-2: polycystin-2; AC6: adenylyl cyclase 6.