Electroneutral uptake and electrogenic secretion of a fluorescent bile salt by rat hepatocyte couplets
| Autor: | James L. Boyer, S. A. Weinman, J. Graf, C. Veith |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Taurocholic Acid
Taurine Physiology Bile Acids and Salts Physiology (medical) Electrochemistry medicine Animals Secretion Ion transporter Ions Membrane potential Oxadiazoles Hepatology biology Chemistry Gastroenterology Biological Transport Depolarization Membrane transport Rats Electrophysiology Perfusion medicine.anatomical_structure Membrane Liver Microscopy Fluorescence Biochemistry Hepatocyte Potassium Biophysics biology.protein Organic anion |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 264:G220-G230 |
| ISSN: | 1522-1547 0193-1857 |
| Popis: | The role of membrane voltage as a driving force for the hepatic uptake and secretion of fluorescent bile salts has been examined in isolated hepatocyte couplets. The present study demonstrates that the fluorescent bile salt derivative (N-[7-(nitrobenz-2-oxa- 1,3-diazol-4-yl)]-7-amino-3 alpha, 12 alpha-dihydroxy-5-cholan-24-oyl)-2-aminoethanesulfonate (7 beta-NBD-NCT) is taken up into hepatocytes by a saturable process with a Kt of 2.7 microM. Uptake rate was reduced by only 22% after total Na+ replacement and was independent of transmembrane potential difference over a range of -135 to +25 mV. In contrast, secretion into the canalicular space was strongly dependent on membrane voltage over the range from -34 to 0 mV in a manner consistent with electrodiffusion of an anion. Fitting the secretion time course to that predicted by electrodiffusion demonstrated that only approximately 50% of total secretion can result from electrodiffusion. Studies in isolated perfused liver confirmed this observation that depolarization caused a decrease in bile salt secretion rate. These results demonstrate that 7 beta-NBD-NCT is transported by a neutral uptake process at the sinusoidal membrane and is secreted across the canalicular membrane in part by electrogenic transport. This suggests that voltage changes could be a common pathway resulting in impaired organic anion secretion in diverse cholestatic syndromes. |
| Databáze: | OpenAIRE |
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