Carbon Tetrachloride Increases Intracellular Calcium in Rat Liver and Hepatocyte Cultures

Sequestration of ionized calcium Ca by rat liver endoplasmic reticulum ER is inhibited following in vivo administration of the hepatotoxin carbon tetrachloride CC14 . Consequently, hepatic cytosolic Ca may rise to supraphysiologic levels, perhaps leading to excessive stimulation of Ca-sensitive processes occurring within liver cells. The hypothesis examined was whether cytoplasmic Ca concentration. are elevated in rat liver and hepatocyte cultures exposed to CCl4 Ca levels were determined indirectly via the Cadependent conversion of glycogen phosphorylase to the form, and directly with the fluorescent Ca-indicator compound quin2. Other biochemical alterations produced by CCl4 were also monitored in order to relate Ca increases to the development of hepatotoxicity. Within half an hour after administration of CCl4 to rats 1.5 mlkg body weight, liver phosphorylase levels increased 136 of control, liver glycogen concentrations decreased 66 of control, and ER Ca pump activity was inhibited 35 of control. These effects persisted through 24 hours. Hepatic glucose-6-phosphatase activity did not decrease until two hours 71 of control, and 5-nucleotidase activity never changed. By eight hours, serum glutamic-pyruvic transaminase activity and total liver calcium levels were elevated 939 and 450 of control, respectively.