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Cholic acid uptake and isolated rat hepatocytes
Hoppe-Seyler'S Zeitschrift Fur Physiologische Chemie
|November 1, 1976
Summary
Hepatocytes transport cholic acid via both simple diffusion and an energy-dependent carrier process. This carrier also interacts with other bile acids, indicating a shared transport mechanism.
Area of Science:
- Hepatobiliary Physiology
- Membrane Transport
- Bile Acid Metabolism
Background:
- Understanding bile acid uptake by hepatocytes is crucial for comprehending liver function and metabolic diseases.
- Cholic acid is a primary bile acid synthesized in the liver, playing a key role in digestion and cholesterol homeostasis.
Purpose of the Study:
- To investigate the mechanisms of cholic acid uptake in isolated rat hepatocytes.
- To characterize the kinetics and identify the nature of the transport process(es) involved.
Main Methods:
- Isolated rat hepatocytes were used with a centrifugal filtration technique for rapid sampling.
- Uptake studies were conducted at various temperatures and substrate concentrations.
- Inhibition studies with oligomycin and KCN, and countertransport experiments were performed.
Main Results:
- Hepatocytes exhibit both adsorption and transport of cholic acid.
- At low temperatures (<10°C), uptake is linear (unsaturable), suggesting simple diffusion.
- Above 10°C, uptake becomes biphasic, revealing a saturable, energy-dependent carrier-mediated process (apparent Km 31µM, Vmax 0.8 nmol/min/mg protein at 37°C) with an activation energy of 13 kcal/mol.
- This saturable process is inhibited by oligomycin and KCN and shows countertransport with other bile acids (taurocholic, chenodeoxycholic).
Conclusions:
- Cholic acid uptake by hepatocytes involves a dual mechanism: simple diffusion and a carrier-mediated, energy-dependent process.
- The identified carrier exhibits affinity for other bile acids, suggesting a role in the overall transport of bile acid conjugates.