AJP - Gastrointestinal and Liver Physiology, Vol 258, Issue 1 73-G77, Copyright © 1990 by American Physiological Society
Hormonal stimulation of Ca2+ release from the perfused liver: effects of uncoupler
N. Kraus-Friedmann, S. Higham and C. R. Fleschner
Department of Physiology and Cell Biology, University of Texas Medical School, Houston 77225.
Administration of vasopressin and glucagon evokes a transient release of
Ca2+ from perfused livers. The Ca2+ is released from a pool that is
depletable by the mitochondrial uncoupler carbonyl cyanide
p-trifluoromethoxyphenylhydrazone (FCCP). Therefore, the mechanism of the
FCCP-stimulated Ca2+ release was examined. The FCCP-stimulated Ca2+ release
was associated with a decrease in ATP levels. In the presence of
oligomycin, which blocked the FCCP-induced rapid ATP breakdown, FCCP did
not release Ca2+ though it still stimulated respiration. The possibility
that FCCP might indirectly cause a release of Ca2+ by lowering hepatic ATP
was examined at two levels of organization: 1) in the whole organ, by
perfusing livers with fructose, a compound that was shown previously to
drastically lower ATP in the liver, and 2) in isolated microsomal vesicles
by depleting ATP with glucose and hexokinase. Fructose evoked Ca2+ release
from the perfused liver. Similarly, depletion of ATP by the addition of
glucose and hexokinase evoked a rapid release of the accumulated Ca2+ from
microsomal vesicles probably by the inhibition of the Ca2(+)-ATPase. These
results demonstrate that the major mechanism by which FCCP releases Ca2+ in
intact cells is by lowering ATP levels.
