Effect of endotoxicosis and sepsis on intracellular calcium homeostasis in rat liver. Mitochondrial and microsomal calcium uptake.
Male rats were treated with endotoxin (ET; Escherichia coli, 026:B6) either acutely (2 mg/100 gm bw, iv) or chronically (0.1 mg/100 gm bw/24 hr from implanted osmotic pumps; [Fish R, Spitzer JA: Circ Shock 12;135, 1984]). At 6 hr after iv injection and at 6, 30, and 100 hr after ET infusion from the pumps, the animals were sacrificed and the livers removed for studies on the respiratory activity (respiratory control index [RCI] with either succinate or malate + glutamate) of isolated mitochondria and Ca uptake as well as Ca content of isolated mitochondria and microsomal vesicles. The same measurements were performed in the livers of rats at 14-16 hr after the onset of peritonitis induced by cecal ligation and perforation. The only changes in RCI specifically ascribable to ET treatment were observed with succinate in continuously infused animals, and they were not associated with changes of mitochondria Ca uptake or content. On the other hand, microsomal Ca uptake was inhibited by ET after both acute and continuous treatment. Neither Ca content nor Ca2+-activated, Mg2+-dependent ATPase in microsomes was affected by ET. No changes in any of these parameters were observed in septic animals. The data suggest that endoplasmic reticulum rather than mitochondria represents the site of interference of ET with intracellular calcium homeostasis in rat liver.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002458:Cell Fractionation; D004731:Endotoxins / Q000494:pharmacology*; D006706:Homeostasis; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000378:metabolism*
D004731:Endotoxins; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D002118:Calcium