Figure 1: Somatostatin treatment decreases cholangiocyte hyperproliferation and fluid hypersecretion in PLD. Hepatic cysts are delineated by bile duct epithelium cells. The primary cilium at the plasma membrane is continuously exposed to luminal bile flow. Mechanical flow rate is sensed by bending the organelle. Under healthy conditions this stimulates calcium signaling and inhibits forskolin-stimulated cAMP signaling intracellularly. PC-2 co-localizes with PC-1, and PC-2 is a calcium channel expressed at the endoplasmatic reticulum. Cholangiocytes possess numerous transporters and exchangers. Basolateral secretin stimulates intracellular cAMP signaling and bicarbonate fluid rich secretion by activation of apical CFTR chloride channel. Subsequently, secreted bicarbonate drives passive AQP1-mediated water transport to the extracellular compartment. This figure illustrates a defective molecular mechanism in PLD. Decreased intracellular calcium and accumulation of second messenger cAMP contributes to hepatic cystogenesis [15]. Phosphorylation of PKA and Epac are associated with increased MAPK/ERK signaling in PLD. In response to this activated pathway fluid secretion and cell proliferation is facilitated [16]. Somatostatin acts via SSTR-2 somatostatin receptors to increase cGMP which inhibits secretin-mediated cAMP synthesis. Secretin-stimulated chloride, bicarbonate and water secretion are inhibited and absorption is induced by somatostatin analogues (in red).