Effect of phenobarbital and 3-methylcholanthrene on biphenyl hydroxylations and fluidity of rat liver microsomal membranes.
The metabolism of biphenyl by rat liver microsomes after administration of phenobarbital and 3-methylcholanthrene was studied. Phenobarbital increased the activity of biphenyl-4-hydroxylase and 3- methylcholanthrene increased the activity of both biphenyl-4-hydroxylase and biphenyl-2-hydroxylase as compared to non-treated (control) rats. Phenobarbital increased the lipid fluidity while 3-methylcholanthrene increased the lipid rigidity of microsomal membranes labeled with 1,6-diphenyl-1,3,5-hexatriene (DPH), as indicated by the steady-state fluorescence anisotropy [(ro/r)-1]-1. Arrhenius plots of [ro/r)-1]-1 indicated that the lipid phase separation of the control membrane at 22.1 +/- 1.1 degrees was reduced in phenobarbital treated (14.5 +/- 0.8 degrees) and increased in 3-methylcholanthrene treated rats (32.7 +/- 2.2 degrees). Arrhenius plots of biphenyl-4-hydroxylase and biphenyl-2-hydroxylase activities exhibited a break point at 21.8 +/- 1.1 degrees and 32.1 +/- 2.1 degrees, respectively, suggesting differences in the interactions of the enzymes with their annular lipids. It is suggested that biphenyl-4-hydroxylase requires a liquid state of its lipid microenvironment to be fully active, while biphenyl-2-hydroxylase a gel state of its lipid microenvironment. These studies provide a basis for postulating that a "non-genomic" mechanism of phenobarbital and 3-methylcholanthrene induces cytochrome P-450 dependent monoxygenases.
Deliconstantinos
G
G
Department of Experimental Physiology, University of Athens, Medical School, Greece.
D000818:Animals; D016880:Anisotropy; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000378:metabolism*; D005453:Fluorescence; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D008748:Methylcholanthrene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013816:Thermodynamics
D001189:Aryl Hydrocarbon Hydroxylases; D001713:Biphenyl Compounds; D008748:Methylcholanthrene; D010634:Phenobarbital; C010574:biphenyl; C021775:biphenyl-2-hydroxylase; C019793:biphenyl-4-hydroxylase