AJP - Regulatory, Integrative and Comparative Physiology, Vol 251, Issue 5 984-R995, Copyright © 1986 by American Physiological Society
Rat liver free cytosolic Ca2+ and glycogen phosphorylase in endotoxicosis and sepsis
I. V. Deaciuc and J. A. Spitzer
Rats were treated with Escherichia coli endotoxin (ET) either acutely or
chronically or rendered septic by cecal ligation and puncture. At 6 h after
ET injection, at various intervals of continuous ET infusion, and at 17-18
h after the onset of peritonitis, animals were killed and hepatocytes were
isolated. Cytosolic [Ca2+] ([Ca2+]c) was measured by quin 2 during the
resting state and after stimulation with epinephrine and vasopressin. Basal
and epinephrine-, vasopressin- and glucagon-stimulated glycogen
phosphorylase activity were also determined. In hepatocytes from acutely
ET-treated rats, resting levels of [Ca2+]c were decreased 46% from 245.8
+/- 11.0 to 131.0 +/- 8.5 nM (n = 4-6, P less than 0.05). In septic rats a
39.5% decrease was noted [i.e., from 154.0 +/- 17.7 (n = 4, sham) to 93.3
+/- 91 nM (n = 5, septic, P less than 0.05)]. These decreased [Ca2+]c
levels were associated with changes of glycogen phosphorylase activity in a
manner suggesting a cause and effect relationship; e.g., acute ET treatment
resulted in greater than 80% depression of phosphorylase a activity,
whereas sepsis induced a 58% decrease in the activity of this enzyme. In
ET-infused rats the resting level of [Ca2+]c and its response to hormonal
stimulation were not different from hepatocytes of saline-infused rats,
although glycogen phosphorylase activity was less responsive to these
hormones. The effect on the enzyme's response to Ca2+-mobilizing hormones
was more marked than to glucagon. This is consistent with the concept that
information flow in the Ca2+-messenger system is a site of metabolic
lesions produced by endotoxicosis and sepsis.
