The effects of volatile anesthetics on Ca++ mobilization in rat hepatocytes.
This study provides direct evidence that in hepatocytes, intracellular Ca++ is released from internal stores by halothane, enflurane, and isoflurane. Hepatocytes isolated from rat livers were used fresh or treated with saponin and then incubated in 45Ca++ media. The uptake of 45Ca++ by hepatocytes was maximal following 13-16 min of incubation (untreated or saponin-treated) and the effects of various agents on the release of 45Ca++ was studied following maximal loading. The agents used included halothane, enflurane, isoflurane, and several putative intracellular second messengers. The anesthetics, to various degrees, all stimulated a significant release of 45Ca++ from internal stores at concentrations that were at or less than clinical concentrations. The release of intracellular 45Ca++ by each of the anesthetic agents was dose-dependent with halothane and enflurane being equally potent at concentrations equivalent to 1 MAC exposure. The halothane-induced release was only somewhat suppressed by preincubation in either 2 mM LaCL3 or 10 microM dantrolene, both suggested Ca++ channel blockers. Transient increases in intracellular Ca++ regulates a number of enzyme systems, including glycogenolysis, while prolonged elevation in Ca++ concentrations have been implicated in the mechanism of hepatotoxicity.
Iaizzo
P A
PA
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905.
Seewald
M J
MJ
Powis
G
G
Van Dyke
R A
RA
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics*; D004737:Enflurane / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D066298:In Vitro Techniques; D007477:Ions; D007530:Isoflurane / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000777:Anesthetics; D007477:Ions; D004737:Enflurane; D007530:Isoflurane; D002118:Calcium; D006221:Halothane