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Solvent isotope effect on bile formation in the rat
C Elsing1, A Hirlinger, E L Renner
1Department of Clinical Pharmacology, University of Berne, Switzerland.
The Biochemical Journal
|April 1, 1995
Summary
Heavy water (2H2O) significantly reduces bile salt-independent bile flow and bicarbonate concentration in rats. This effect is linked to the inhibition of canalicular chloride/bicarbonate exchange, impacting bile formation.
Area of Science:
- Physiology
- Biochemistry
- Membrane Transport
Background:
- 2H2O influences membrane transport via solvent and kinetic isotope effects.
- Bile formation involves osmotic filtration, making it susceptible to such effects.
Purpose of the Study:
- To investigate the impact of 2H2O on bile formation in a perfused rat liver model.
- To determine the specific mechanisms by which 2H2O affects bile composition and flow.
Main Methods:
- In situ perfused rat liver model to assess bile formation.
- In vitro studies on canalicular membrane vesicles and specific proteins.
- Dose-finding experiments to establish optimal 2H2O concentration.
Main Results:
- 60% 2H2O reduced bile salt-independent bile flow by approximately 33% and biliary bicarbonate concentration by 40%.
- 2H2O inhibited canalicular Cl-/HCO(3-)-exchange by 50% at 60% concentration.
- No alteration in choleretic response to bile acids was observed.
Conclusions:
- 2H2O inhibits bile salt-independent bile flow, primarily by affecting canalicular Cl-/HCO(3-)-exchange.
- The findings suggest a role for altered bicarbonate transport in 2H2O-induced changes in bile formation.
- Further research is needed to clarify the precise role of hydration in these effects.