An electrophilic affinity ligand based on (+)-MK801 distinguishes PCP site 1 from PCP site 2

Hyacinth C. Akunne, J. A. Monn, Andrew Thurkauf, Arthur E. Jacobson, Kenner C. Rice, Joannes T.M. Linders, Q. Jiang, F. Porreca, Richard B. Rothman

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The electrophilic affinity ligand, (+)-3-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine hydrochloride {(+)-MK801-NCS} was characterized for its ability to acylate phencyclidine (PCP) and sigma binding sites in vivo. Initial studies, conducted with mouse brain membranes, characterized the binding sites labeled by [3H]1-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP). The Kd values of [3H]TCP for PCP site 1 (MK801-sensitive) and PCP site 2 (MK801-insensitive) were 12 nM and 68 nM, with Bmax values of 1442 and 734 fmol/mg protein, respectively. Mice were sacrificed 18-24 hours following intracerebroventricular administration of the acylator. The administration of (+)-MK801-NCS increased [3H]TCP binding to site 2, but not to site. 1. Although (+)-MK801-NCS decreased [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d; cbcyclohepten-5,10-imine maleate ([3H](+)-MK801) binding to site 1, it had no effect on [3H]TCP binding to site 1. Viewed collectively with other published data, these data support the hypothesis that PCP sites 1 and 2 are distinct binding sites, and that [3H]TCP and [3H](+)-MK801 label different domains of the PCP binding site associated with the NMDA receptor.

Original languageEnglish (US)
Pages (from-to)385-389
Number of pages5
JournalNeurochemical Research
Volume19
Issue number4
DOIs
StatePublished - Apr 1 1994

Keywords

  • (+)-MK801
  • 1,3-di(2-tolyl)guanidine
  • N-methyl-D-aspartate
  • PCP
  • affinity ligands
  • sigma receptors

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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  • Cite this

    Akunne, H. C., Monn, J. A., Thurkauf, A., Jacobson, A. E., Rice, K. C., Linders, J. T. M., Jiang, Q., Porreca, F., & Rothman, R. B. (1994). An electrophilic affinity ligand based on (+)-MK801 distinguishes PCP site 1 from PCP site 2. Neurochemical Research, 19(4), 385-389. https://doi.org/10.1007/BF00967314