Hepatic Bile Formation: Canalicular Osmolarity and Paracellular and Transcellular Water Flow
Raul A Marinelli1, Mary Vore1, Norman B Javitt2
1Instituto de Fisiologia Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Santa Fe, Argentina (R.A.M.); Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, Kentucky (M.V.); and Department of Medicine and Pediatrics, New York University School of Medicine, New York, New York (N.B.J.).
The Journal of Pharmacology and Experimental Therapeutics
|October 2, 2019
Summary
Hepatic bile flow is not solely driven by bile acid transport. New research shows independent regulation of water channels and tight junctions, challenging previous models of cholestasis.
Area of Science:
- Hepatology
- Physiology
- Molecular Biology
Background:
- Bile acid and solute transport historically viewed as primary drivers of hepatic bile flow via osmotic gradients.
- Transcellular and paracellular routes for water movement into canaliculi were considered passive consequences of solute transport.
Purpose of the Study:
- To present a new paradigm in hepatic bile flow regulation.
- To highlight the independent regulation of water channels and tight junctions in bile canaliculi.
Main Methods:
- Review of existing literature and recent experimental findings.
- Analysis of data from Claudin-2 knockout mice and studies involving estradiol 17β-d-glucuronide.
Main Results:
- Hepatic water flow into canaliculi is regulated independently of bile acid transport.
- Tight junctions (paracellular) and Aquaporin-8 water channels (transcellular) exhibit independent regulation.
- Reduced paracellular or transcellular water flow does not significantly impact bile acid excretion.
Conclusions:
- The established model of hepatic bile flow requires revision.
- Independent regulation of water channels and tight junctions offers new insights into cholestasis.
- Future research should focus on these distinct determinants of bile flow.
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