Hormonal stimulation of Ca2+ release from the perfused liver: effects of uncoupler.
Administration of vasopressin and glucagon evokes a transient release of Ca2+ from perfused livers. The Ca2+ is released from a pool that is depletable by the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). Therefore, the mechanism of the FCCP-stimulated Ca2+ release was examined. The FCCP-stimulated Ca2+ release was associated with a decrease in ATP levels. In the presence of oligomycin, which blocked the FCCP-induced rapid ATP breakdown, FCCP did not release Ca2+ though it still stimulated respiration. The possibility that FCCP might indirectly cause a release of Ca2+ by lowering hepatic ATP was examined at two levels of organization: 1) in the whole organ, by perfusing livers with fructose, a compound that was shown previously to drastically lower ATP in the liver, and 2) in isolated microsomal vesicles by depleting ATP with glucose and hexokinase. Fructose evoked Ca2+ release from the perfused liver. Similarly, depletion of ATP by the addition of glucose and hexokinase evoked a rapid release of the accumulated Ca2+ from microsomal vesicles probably by the inhibition of the Ca2(+)-ATPase. These results demonstrate that the major mechanism by which FCCP releases Ca2+ in intact cells is by lowering ATP levels.
Kraus-Friedmann
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N
Department of Physiology and Cell Biology, University of Texas Medical School, Houston 77225.
Higham
S
S
Fleschner
C R
CR
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D009840:Oligomycins / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000494:pharmacology*
D009570:Nitriles; D009840:Oligomycins; D014667:Vasopressins; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000001:Calcimycin; D005934:Glucagon; D002118:Calcium