Alterations in cellular Ca2+ regulation in the liver in endotoxic shock.
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.
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D007474:Ion Exchange; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000378:metabolism*
D002118:Calcium; D009638:Norepinephrine