Ca2+ mobilization by vasopressin and glucagon in perfused livers. Effect of prior intoxication with bromotrichloromethane.
Perfused livers isolated from rats treated with BrCCl3 for up to 15 min were used as an experimental tool to investigate the role of the hepatic endoplasmic reticulum in Ca2+ mobilization elicited by vasopressin and glucagon. BrCCl3-treatment caused extensive impairment (37 to 92%) of Ca2+ pumps of isolated liver microsomes, while Ca2+ pumps of mitochondria and plasma membrane vesicles remained undamaged. In perfused livers of BrCCl3-treated rats, the efflux of Ca2+ and the concomitant stimulation of O2 consumption and glucose release induced by vasopressin were decreased. The extent of the decrease paralleled the duration of BrCCl3-treatment. The decrease of Ca2+ efflux following vasopressin addition was closely correlated with the decrease of active Ca2+ accumulation by isolated microsomes (r = 0.99, P less than 0.001). The Ca2+ efflux elicited by glucagon was also decreased after BrCCl3-treatment, whereas stimulation of O2 consumption and glucose release were retained. The possibility that BrCCl3-treatment might impair the production of the intracellular Ca2+-mobilizing messenger IP3 is unlikely, since vasopressin still induced the formation of inositol phosphates, including IP3, in isolated hepatocytes obtained from BrCCl3-treated rats. Thus, this work supports the hypothesis that the Ca2+ stored in the liver ER is the major pool of intracellular Ca2+ available for mobilization by vasopressin, glucagon and other effectors.
Benedetti
A
A
Institute of General Pathology, University of Siena, Italy.
Graf
P
P
Fulceri
R
R
Romani
A
A
Sies
H
H
D000818:Animals; D001975:Bromotrichloromethane / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002725:Chloroform / Q000031:analogs & derivatives*; D005934:Glucagon / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D008862:Microsomes, Liver / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000494:pharmacology*
D007295:Inositol Phosphates; D014667:Vasopressins; D002725:Chloroform; D005934:Glucagon; D001975:Bromotrichloromethane; D005947:Glucose; D002118:Calcium