AJP - Gastrointestinal and Liver Physiology, Vol 249, Issue 4 427-G433, Copyright © 1985 by American Physiological Society
Effect of glucagon on hepatic taurocholate uptake: relationship to membrane potential
J. W. Edmondson, B. A. Miller and L. Lumeng
Since glucagon can hyperpolarize hepatic plasma membrane and stimulate
biliary bile acid secretion in vitro, we studied the effect of glucagon on
taurocholate uptake and its relationship to plasma membrane potential in
isolated rat hepatocytes. [14C]taurocholate uptake was linear through 1 min
and contained a saturable sodium-dependent and a nonsaturable
sodium-independent component. Km of taurocholate uptake by the
sodium-dependent system was 18.4 microM. Hill coefficient for Na+ was 2.59
and for taurocholate was 1.1, suggesting that the stoichiometry is 2 Na+:1
bile acid. Stimulation of taurocholate uptake by glucagon was limited to
the sodium-dependent component, detected within 5 min of hormone exposure,
and was maximum at 30 min. Glucagon, from 10(-8) to 10(-5) M, stimulated
taurocholate uptake and hyperpolarized concurrently the plasma membrane
potential. Because valinomycin produced a dose-related depolarization of
plasma membrane potential, this agent was used to counteract the effects of
glucagon. With 10(-6) M glucagon, valinomycin (10(-10) M) depolarized
membrane potential from -35.50 to -28.00 mV and inhibited taurocholate
uptake from 60% above the control rate to 5% below. These data strongly
suggest that taurocholate uptake by isolated hepatocytes is an electrogenic
process, and its stimulation by glucagon may be mediated by changes in
plasma membrane potential.
