Release of calcium from the endoplasmic reticulum by bile acids in rat liver cells.
The effects of four bile acids on cell Ca2+ were examined in suspensions of isolated rat hepatocytes. Taurolithocholate and lithocholate which inhibit bile secretion increased the cytosolic Ca2+ concentration (ED50, 25 microM), as measured by the fluorescent indicator quin2, and promoted a net loss of Ca2+ from the cells. This effect resulted from rapid mobilization of Ca2+ from an intracellular Ca2+ store. This store corresponds to the one that is permeabilized by the inositol (1,4,5)trisphosphate-dependent hormone vasopressin. However, taurolithocholate and lithocholate, unlike the hormone, did not induce a significant accumulation of inositol trisphosphate fraction in isolated hepatocytes. In addition, these agents did not alter the cell and the mitochondria membrane permeability to ions. When applied to saponin-permeabilized cells, taurolithocholate and lithocholate released Ca2+ (ED50, 20 microM) from an ATP-dependent, nonmitochondrial pool which is sensitive to inositol (1,4,5)trisphosphate. In contrast, the bile acids taurocholate and cholate, which increase bile secretion, had no effect on cell Ca2+ in intact hepatocytes or in saponin-permeabilized hepatocytes. It is suggested that taurolithocholate and lithocholate permeabilize the endoplasmic reticulum to Ca2+ and that the resulting permeabilization of this compartment may be involved in the inhibition of bile secretion in mammalian liver.
Combettes
L
L
Institut National de la Santé et de la Recherche Médicale, U. 274, Université Paris-Sud, Orsay, France.
Dumont
M
M
Berthon
B
B
Erlinger
S
S
Claret
M
M
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000494:pharmacology; D008095:Lithocholic Acid / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012503:Saponins / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D001647:Bile Acids and Salts; D007295:Inositol Phosphates; D012503:Saponins; D014667:Vasopressins; D013656:Taurocholic Acid; D008095:Lithocholic Acid; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium