Inhibition of liver endoplasmic reticulum calcium pump by CCl4 and release of a sequestered calcium pool.
One of the earliest effects observed in rat liver after CCl4 administration is inhibition of an ATP-dependent calcium pump found at the endoplasmic reticulum. This report confirms that the amount of calcium associated with the microsomal fraction is reduced after CCl4 administration and, for the first time, demonstrates time-, dose-, and metabolism-dependent relationships between inhibition of the liver microsomal calcium pump and the amount of calcium found in the microsomal fraction. Furthermore, release of calcium from the endoplasmic reticulum is shown to cause activation of a cytoplasmic enzyme that responds to increases of ionized calcium, glycogen phosphorylase. This suggests that the endoplasmic reticulum calcium pump sequesters an intracellular pool of calcium within the endoplasmic reticulum. This pool of calcium may be released into the cytoplasm as a consequence of inhibition of the calcium pump by CCl4.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002725:Chloroform / Q000633:toxicity; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010762:Phosphorylase a / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D007473:Ion Channels; D002725:Chloroform; D002251:Carbon Tetrachloride; D000242:Cyclic AMP; D010762:Phosphorylase a; D002118:Calcium