Fluid flow induces mechanosensitive ATP release, calcium signalling and Cl- Transport in biliary epithelial cells through a PKCζ-dependent pathway

Kangmee Woo, Amal K. Dutta, Vishal Patel, Charles Kresge, Andrew P. Feranchak

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

ATP in bile is a potent secretogogue, stimulating cholangiocyte Cl- and fluid secretion via binding to membrane P2 receptors, though the physiological stimuli involved in biliary ATP release are unknown. The goal of the present studies was to determine the potential role of fluid flow in biliary ATP release and secretion. In both human Mz-Cha-1 biliary cells and normal rat cholangiocyte monolayers, exposure to flow increased relative ATP release which was proportional to the shear stress. In parallel studies, shear was associated with an increase in [Ca2+]i and membrane Cl- permeability, which were both dependent on extracellular ATP and P2 receptor stimulation. Flow-stimulated ATP release was dependent on [Ca2+]i, exhibited desensitization with repetitive stimulation, and was regulated by PKCζ. In conclusion, both human and rat biliary cells exhibit flow-stimulated, PKCζ-dependent, ATP release, increases in [Ca2+]i and Cl- secretion. The finding that fluid flow can regulate membrane transport suggests that mechanosensitive ATP release may be a key regulator of biliary secretion and an important target to modulate bile flow in the treatment of cholestatic liver diseases.

Original languageEnglish (US)
Pages (from-to)2779-2798
Number of pages20
JournalJournal of Physiology
Volume586
Issue number11
DOIs
StatePublished - Jun 1 2008

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Calcium Signaling
Adenosine Triphosphate
Epithelial Cells
Bile
Membranes
Purinergic P2 Receptors
Fluids and Secretions
Liver Diseases
Permeability

ASJC Scopus subject areas

  • Physiology

Cite this

Fluid flow induces mechanosensitive ATP release, calcium signalling and Cl- Transport in biliary epithelial cells through a PKCζ-dependent pathway. / Woo, Kangmee; Dutta, Amal K.; Patel, Vishal; Kresge, Charles; Feranchak, Andrew P.

In: Journal of Physiology, Vol. 586, No. 11, 01.06.2008, p. 2779-2798.

Research output: Contribution to journalArticle

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