Is there a pleiotropic response in barbiturate induction?
C57BL/6J mice were treated with barbitone, phenobarbitone, thiopentone and hexobarbitone, respectively, for a period of 6 days, and the resulting induction effects compared. Among parameters measured were metabolic rates for ethylmorphine, biphenyl, ethoxycoumarin and pentoxyresorufin. Effects of inducers were easily distinguishable from each other. No fixed proportions were seen among increased metabolic rates, but increases of relative liver weight, cytochrome P450 per g liver and pentoxyresorufin metabolism were accompanied by a corresponding decrease of biphenyl-2-hydroxylation. Doubling the dose (NMRI mice) of hexobarbitone and thiopentone increased inductive responses, but did not render them more similar to each other. Pentoxyresorufin metabolism was increased 5- to 30-fold, calculated per nmol cytochrome P450. The results argue against the existence of one pleiotropic response--at least in a strict sense--in barbiturate induction.
D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009929:Organ Size / Q000187:drug effects; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D001463:Barbiturates; D003577:Cytochrome P-450 Enzyme System