AJP - Regulatory, Integrative and Comparative Physiology, Vol 250, Issue 5 884-R891, Copyright © 1986 by American Physiological Society
Alterations in cellular Ca2+ regulation in the liver in endotoxic shock
M. M. Sayeed
Effects of Salmonella enteritidis endotoxin on cellular Ca2+ regulation
were studied in the liver. Rats were given intravenous injections of saline
(control) or endotoxin (15 mg/kg). They were killed 5 h later, at which
time endotoxin-injected rats showed signs of shock. Liver slices were used
to measure Ca2+ efflux from the intracellular Ca2+ pool and the size of
that pool. 45Ca uptake was measured in isolated endoplasmic reticulum (ER)
from livers. 45Ca efflux and uptake were also measured in control liver
slices and ER in the presence of endotoxin (250 micrograms/ml) in vitro. In
control livers, 45Ca efflux from the intracellular pool was sensitive to
iodoacetate and 45Ca uptake by ER was ATP dependent. These active Ca2+
movements were significantly attenuated by endotoxin in vitro but were
unaltered in livers of endotoxic rats. However, the intracellular Ca2+ pool
size and norepinephrine (NE) regulation of cellular Ca2+ were adversely
affected in endotoxic shock. Though the application of 1 microM NE to
control liver slices significantly stimulated 45Ca efflux, it failed to
stimulate efflux in liver slices of endotoxic rats. The intracellular Ca2+
pool in endotoxic livers (mean +/- SE = 553 +/- 23 mumol/kg tissue) was
significantly larger than in controls (413 +/- 17). These results suggest
that during endotoxic shock there is a depletion of the NE-mobilized
activator Ca2+ in liver that could lead to a failure of alpha-adrenergic
stimulation of hepatic glucose production. The increased sequestration of
Ca2+ in the intracellular pool in endotoxic rat liver cells could be due to
an influx of extracellular Ca2+ and may predispose these cells to Ca2+
overload.
