Discrepancies in characterization of σ sites in the mouse central nervous system

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Abstract

The characteristics of [3H](+)-pentazocine and [3H]1,3-di(2-tolyl)guanidine (DTG) binding to mouse whole brain, cortex, cerebellum and spinal cord membranes were investigated in radioreceptor assays. [3H](+)-Pentazocine bound to a single, high affinity site (Kd = 1.2 - 1.6 nM) with increasing density along the neuraxis from the cortex (Bmax = 543 fmol/mg protein) to the spinal cord (Bmax = 886 fmol/mg protein). Hot saturation studies resolved the presence of one binding site for [3H]DTG showing no tissue variations in terms of density (Bmax = 1075-1264 fmol/mg protein) or affinity (Kd = 16.6-22.3 nM). Incubation with 100 nM (+)-pentazocine revealed two classes of high affinity [3H]DTG labeled binding sites corresponding to σ1 and σ2 subtypes. A preponderance of σ2 sites was revealed in all investigated tissues. Different pharmacological profiles were demonstrated for the σ2 sites in mouse whole brain compared to mouse spinal cord. However, competition studies indicated that the whole brain and spinal [3H](+)-pentazocine labeled σ1 binding sites exhibited similar pharmacological properties. The density of [3H](+)-pentazocine labeled σ1 population was found not to match that of [3H]DTG labeled σ1 site throughout the mouse central nervous system. The presence of low affinity [3H]DTG labeled sites was demonstrated in cold saturation experiments. Equilibrium binding data for the low affinity [3H]DTG binding site resulted in an increasing density (Bmax = 1973-11369 fmol/mg protein) with a decreasing affinity (Kd = 242-943 nM) in mouse cortex through the spinal cord.

Original languageEnglish (US)
Pages (from-to)127-134
Number of pages8
JournalEuropean Journal of Pharmacology
Volume285
Issue number2
DOIs
StatePublished - Oct 16 1995

Keywords

  • (+)-Pentazocine
  • (Mouse)
  • Brain
  • DTG (1,3-di(2-tolyl)guanidine)
  • Radioreceptor assay
  • Spinal cord
  • σBinding site, heterogeneity

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