AJP - Gastrointestinal and Liver Physiology, Vol 255, Issue 5 547-G555, Copyright © 1988 by American Physiological Society
Hepatic efflux of glutathione by the perfused rat liver: role of membrane potential difference
T. L. Wright, J. G. Fitz and T. D. Boyer
Liver Studies Unit, Veterans Administration Medical Center, San Francisco, California.
Glutathione (GSH) is released into hepatic sinusoids by a carrier-mediated
process. The importance of transmembrane potential difference (PD) as a
driving force for hepatic efflux of GSH from isolated perfused rat liver
was investigated. The membrane PD was measured using intracellular
microelectrodes as PD was altered over the physiological range by ion
substitution in the perfusate. The effect of a change in membrane PD on the
rate of efflux of GSH into the perfusate was determined. Because GSH
carries a net negative charge at physiological values of pH, we predicted
that hyperpolarization of cells would increase efflux, whereas
depolarization would decrease efflux. Three different manipulations were
used to depolarize the hepatocyte membrane to a similar degree, and
variable effects on GSH efflux were observed. Substitution of Cl with
gluconate in the perfusate depolarized the hepatocyte but had no effect on
GSH efflux, whereas substitution of Na with choline in the perfusate
increased GSH efflux to 110% of basal values. Perfusion with K+ inhibited
GSH efflux by 21%. The latter two manipulations were associated with
evidence of hepatic injury. Hyperpolarization of the hepatocyte also had
variable effects on GSH efflux. Substitution of Cl with nitrate in the
perfusate transiently increased the membrane PD and decreased GSH efflux,
whereas perfusion with glucagon caused a sustained increase in membrane PD
but did not alter GSH efflux rates. None of the latter manipulations was
associated with hepatic injury and thus no consistent relationship between
membrane PD and sinusoidal efflux of GSH was demonstrated. We conclude that
in the isolated perfused rat liver, efflux of GSH is not driven directly by
membrane PD.
