Allosteric modulation of ligand binding to [ 3H](+)pentazocine-defined σ recognition sites by phenytoin

• Published in: Life sciences (1973) Vol. 53; no. 1; pp. 41 - 48
• Main Authors: DeHaven-Hudkins, D.L., Ford-Rice, F.Y., Allen, J.T., Hudkins, R.L.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 1993; Elsevier
• Subjects: Allosteric Regulation; Animals; Binding Sites; Biological and medical sciences; Cell receptors; Cell structures and functions; Cyclopentanes - metabolism; Dextromethorphan - metabolism; Dextrorphan - metabolism; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Ligands; Male; Miscellaneous; Molecular and cellular biology; Pentazocine - metabolism; Phenazocine - analogs & derivatives; Phenazocine - metabolism; Phenytoin - pharmacology; Piperidines - metabolism; Radioligand Assay; Receptors, sigma - drug effects; Receptors, sigma - metabolism; Tritium; Ligand binding; Vertebrata; Mammalia; Guinea pig; Allosteric regulation; Rodentia; Central nervous system; Sigma receptor; Brain (vertebrata)
• DOI: 10.1016/0024-3205(93)90609-7
• ISSN: 0024-3205

The allosteric modulation of σ recognition sites by phenytoin (diphenylhydantoin) has been demonstrated by the ability of phenytoin to stimulate binding of various [ 3H]σ ligands, as well as to slow dissociation from σ sites and to shift σ sites from a low- to a high-affinity state. Phenytoin stimulated the binding of the σ 1-selective ligand [ 3H](+)pentazocine in a dose-dependent manner. Stimulation of binding at a final concentration of 250 μM phenytoin was associated with a decrease in the K D. The affinities of the σ reference compounds caramiphen, dextromethorphan, dextrorphan, (+)3-PPP and (+)SKF-10.047 were three- to eight-fold higher, while the affinities of benzetimide, BMY-14802, carbetapentane, DTG and haloperidol were unchanged in the presence of 250 μM phenytoin. The relative sensitivity of σ compounds to allosteric modulation by phenytoin is not a property of all σ ligands, and may provide an in vitro basis for distinguishing actions of σ compounds and predicting σ effects in vivo.