Differential effects of cytochrome P-450 induction on ligand binding to sigma receptors.
The identity of the sigma receptor as a form of cytochrome P-450 was investigated in rats treated with 3-methylcholanthrene or phenobarbital. The density of [3H]N,N'-di(o-tolyl)guanidine (DTG) binding to sigma 2 receptors in hepatic subcellular fractions increased following both treatments, while [3H](+)-pentazocine binding to sigma 1 receptors was unchanged. Furthermore, proadifen and piperonyl butoxide inhibited [3H](+)-pentazocine and [3H]DTG binding with low potency. The low affinity of cytochrome P-450 inhibitors for sigma receptors, the similar degree of enhancement of [3H]DTG binding by agents with disparate cytochrome P-450 induction profiles and the lack of change in [3H](+)-pentazocine binding are inconsistent with the identity of the sigma receptor as a cytochrome P-450.
Basile
A S
AS
Laboratory of a Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892.
Paul
I A
IA
de Costa
B
B
D000818:Animals; D001921:Brain / Q000201:enzymology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D019791:Guanidine; D006146:Guanidines / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D010423:Pentazocine / Q000493:pharmacokinetics; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000032:analysis / Q000187:drug effects*; D013347:Subcellular Fractions; D014316:Tritium
D006146:Guanidines; D017480:Receptors, sigma; D014316:Tritium; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D019791:Guanidine; D010423:Pentazocine; D010634:Phenobarbital