The effects of halothane on hepatic microsomal electron transfer.
1. The effects of halothane (CF3CHBrCl), a volatile anaesthetic agent, on electron transfer in isolated rat liver microsomal preparations were examined. 2. At halothane concentrations achieved in tissues during clinical anaesthesia (1-2mM), halothane shifts the redox equilibrium of microsomal cytochrome b5 in the presence of NADPH towards the oxidized form. Halothane accelerates stoicheiometric consumption of NADPH and O2, increases the rate of reoxidation of NADH-reduced microsomal ferrocytochrom b5, but does not affect NADPH- or NADH-cytochrome c reductase activity. The enhanced microsomal electron flow seen in the presence of halothane is not diminished by CO nor is it increased by pretreatment of the animals with phenobarbital. 3. The effects of halothane are maximum in microsomal preparations isolated from animals fed on a high-carbohydrate diet to induce stearate desaturase activity. Changes in microsomal electron transfer caused by halothane are in all cases abolished by low concentrations (1-2mM) of cyanide. Microsomal stearate desaturase activity is unaffected by halothane. 4. The first-order rate constant for oxidation of membrane-bound ferrocytochrome b5 in the absence of added substrate (k1 equals 1.5 times 10(-3)A-1) is similar to that for autoxidation of purified ferrocytochrome b5(k1 equals 7 times 10(-3)S-1) the rate of autoxidation of soluble ferrocytochrome b5 is unaffected by halothane. 5. It is concluded that the effects of halothane on microsomal electron transfer are not related to cytochrome P-450 linked metabolism but rather arise from the interaction of halothane with the cyanide-sensitive factor of the stearate desaturase pathway.
D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology; D003486:Cyanides / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003579:Cytochrome Reductases / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects*; D003576:Electron Transport Complex IV / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism
D003486:Cyanides; D003580:Cytochromes; D009243:NAD; D009249:NADP; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D013230:Stearoyl-CoA Desaturase; D003579:Cytochrome Reductases; D003576:Electron Transport Complex IV; D006221:Halothane; D010634:Phenobarbital