Selective inactivation of rat and bovine olfactory cytochrome P450 by three haloethanes.
The effects of halothane, 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123) and 1,1-dichloro-1-fluoroethane (HCFC-141b) on the P450 system in olfactory and hepatic microsomes of bovine and rat have been investigated. In the in vitro experiments, all three compounds decreased olfactory CYP-dependent activities in microsomes from both species, especially under anaerobic conditions, halothane showing the greatest effect. Hepatic activities were not affected. A selective olfactory CYP depletion was also observed in vivo after treatment with halothane, but not with HCFC-123 or HCFC-141b. A loss of olfactory ethoxycoumarin-O-deethylase activity was also found both in vitro and in vivo experiments, suggesting that a CYP2A isoform may be the main target of inactivation. The present results therefore suggest that CYP2A, the major isoform expressed in the olfactory tissue of mammals, may be particularly prone to catalyze the reductive metabolism of halothane both in anaerobic and aerobic conditions.
Marini
S
S
Istituto di Mutagenesi e Differenziamento, CNR, Area della Ricerca-Via Moruzzi, via Svezia 10, 56124 Pisa, Italy.
Longo
V
V
Zaccaro
C
C
De Matteis
F
F
Gervasi
P G
PG
D018685:Anesthetics, Inhalation / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D002384:Catalysis; D002417:Cattle; D017402:Chlorofluorocarbons / Q000009:adverse effects* / Q000494:pharmacology; D064227:Chlorofluorocarbons, Ethane; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006221:Halothane / Q000009:adverse effects* / Q000494:pharmacology; D007527:Isoenzymes; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009666:Nose / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018685:Anesthetics, Inhalation; D017402:Chlorofluorocarbons; D064227:Chlorofluorocarbons, Ethane; D007527:Isoenzymes; C067411:2,2-dichloro-1,1,1-trifluoroethane; D003577:Cytochrome P-450 Enzyme System; C068320:1,1-dichloro-1-fluoroethane; D006221:Halothane