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Water movement across rat bile duct units is transcellular and channel‐mediated
Author(s) -
Cova Emanuela,
Gong AiYu,
Marinelli Raul A.,
LaRusso Nicholas F.
Publication year - 2001
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2001.27092
Subject(s) - forskolin , choleretic , paracellular transport , endocrinology , chemistry , medicine , cholangiocyte , transcellular , water transport , apical membrane , biophysics , water flow , biology , biochemistry , permeability (electromagnetism) , membrane , receptor , environmental engineering , engineering
In recent studies using freshly isolated rat cholangiocytes, we established that water crosses the cholangiocyte membrane by a channel‐mediated mechanism involving aquaporins, a family of water‐channel proteins. Our goal was to address the importance of channel‐mediated water transport in ductal bile formation by employing a physiologic experimental model, the enclosed, polarized rat intrahepatic bile duct unit (IBDU). Expansion and reduction of luminal areas as a reflection of water movement into and out of IBDUs prepared from livers of normal rats were measured by quantitative computer‐assisted image analysis. When enclosed IBDUs were exposed to inward or outward osmotic gradients, their luminal area rapidly increased (approximately 25%) or decreased (approximately 20%) reflecting net water secretion or absorption, respectively. These effects were specifically inhibited by 2 water channel blockers, DMSO and HgCl 2 . In both instances, β‐mercaptoethanol reversed the inhibitory effects. In the absence of an osmotic gradient, choleretic agents (secretin and forskolin) and a cholestatic hormone (somatostatin) induced a significant increase or decrease of IBDU luminal area by 21% and 22%, respectively. These effects were also inhibited by DMSO and reversed by β‐mercaptoethanol. Under our experimental conditions, DMSO did not interfere with either forskolin‐induced cAMP synthesis or the generation of osmotic driving forces via the apical chloride‐bicarbonate exchanger. Protamine, an inhibitor of the paracellular pathway, had no effect on hypotonic or forskolin‐induced water secretion in IBDUs. These results in a physiologically relevant model of ductal bile formation provide additional support for the concept that osmotically driven and agonist‐stimulated water movement into (secretion) and out of (absorption) the biliary ductal lumen is transcellular and water channel‐mediated. (H EPATOLOGY 2001;34:456‐463.)