AJP - Gastrointestinal and Liver Physiology, Vol 245, Issue 3 399-G403, Copyright © 1983 by American Physiological Society
Amino acid inhibition of bile acid uptake by isolated rat hepatocytes: relationship to dissipation of transmembrane Na+ gradient
B. L. Blitzer, S. L. Ratoosh and C. B. Donovan
The effects of amino acids on bile acid uptake were studied in isolated rat
hepatocytes. The Na+-dependent amino acid L-alanine inhibited
[14C]taurocholate uptake in a nonlinear fashion (IC50, approximately 7 mM).
Kinetic studies showed that alanine (30 mM) reduced the Vmax for
taurocholate uptake from 1.7 +/- 0.1 to 1.1 +/- 0.1 nmol . mg protein-1 .
min-1 but did not significantly affect taurocholate Km (42 +/- 7 vs. 35 +/-
7 microM). Taurocholate uptake was also inhibited by
alpha-methylaminoisobutyric acid (which shares a common Na+-dependent
transport pathway with alanine but is not metabolized) and by L-glutamine
(undergoes Na+-dependent hepatic uptake via a carrier distinct from that
for alanine). In contrast, the Na+-independent amino acid
2-aminobicyclo(2,2,1)heptane-2-carboxylic acid had no effect on hepatocyte
bile acid uptake. Alanine induced a twofold elevation of intracellular
sodium concentration as determined by the steady-state uptake of 22Na.
These findings suggest that Na+-dependent amino acids noncompetitively
inhibit hepatocyte taurocholate uptake by dissipating the transmembrane Na+
gradient and thereby reduce the driving forces for Na+-coupled bile acid
entry. Dissipation of the Na+ gradient by substrates that undergo
Na+-dependent hepatic transport may represent a novel mechanism of bile
secretory failure.
