Regulated ion transport in mouse liver cyst epithelial cells.
Derived from bile duct epithelia (BDE), secretion by liver cyst-lining epithelia is positioned to drive cyst expansion but the responsible ion flux pathways have not been characterized. Cyst-lining epithelia were isolated and cultured into high resistance monolayers to assess the ion secretory pathways. Electrophysiologic studies showed a marked rate of constitutive transepithelial ion transport, including Cl(-) secretion and Na(+) absorption. Na(+) absorption was amiloride-sensitive, suggesting the activation of epithelial sodium channels (ENaC). Further, both cAMP(i) and extracellular ATP induced robust secretory responses. Western blotting and immunohistologic analysis of liver cyst epithelia demonstrated expression of P2X4, a potent purinergic receptor in normal BDE. Luminometry and bioassaying measured physiologically relevant levels of ATP in a subset of liver cyst fluid samples. Liver cyst epithelia also displayed a significant capacity to degrade extracellular ATP. In conclusion, regulated ion transport pathways are present in liver cyst epithelia and are positioned to direct fluid secretion into the lumen of liver cysts and promote increases in liver cyst expansion and growth.
Doctor
R Brian
RB
Division of Gastroenterology, University of Colorado Health Sciences Center, Box B158, 4200 E. 9th Avenue, Denver, CO 80262, USA. brian.doctor@uchsc.edu
Johnson
Sylene
S
Brodsky
Kelley S
KS
Amura
Claudia R
CR
Gattone
Vincent
V
Fitz
J Gregory
JG
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001652:Bile Ducts / Q000378:metabolism* / Q000473:pathology; D002713:Chlorine / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D003560:Cysts / Q000737:chemistry / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D017136:Ion Transport; D008113:Liver Neoplasms / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058848:Receptors, Purinergic P2X4; D012964:Sodium / Q000378:metabolism
D053503:Epithelial Sodium Channels; C548227:P2rx4 protein, mouse; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; D002713:Chlorine; D000584:Amiloride; D000255:Adenosine Triphosphate; D012964:Sodium; D000242:Cyclic AMP