Carbon Tetrachloride Increases Intracellular Calcium in Rat Liver and Hepatocyte Cultures.

摘要

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 Ca++_dependent 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 ml/kg 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).