Absence of modifications of the pharmacological properties of the GABAA receptor complex during aging, as assessed in 3- and 24-month-old rat cerebral cortex

Eur J Pharmacol. 1993 Jun 15;246(1):81-7. doi: 10.1016/0922-4106(93)90013-y.

Abstract

We have investigated the possible modifications of the pharmacological properties of Type I and Type II benzodiazepine binding sites of the gamma-aminobutyric acidA (GABAA) receptor complex in cortical membranes from 3- and 24-month-old Wistar or Fischer rats. No major changes were found in the binding parameters of [3H]zolpidem (a Type I-specific ligand) or [3H]flunitrazepam (a non-selective benzodiazepine). Neither the Kd values nor the Bmax for either ligand were modified during aging in cortical membranes from Wistar or Fischer rats. Consequently, the proportion of Type I binding sites was also unmodified in aged cortical membranes. The absence of modifications of Type I and Type II binding sites was also confirmed by Cl 218,872 displacement of [3H]flunitrazepam binding in aged cortical membranes from Wistar rats. Furthermore, the [3H]muscimol binding and the allosteric interactions between Type I or total benzodiazepine binding sites and GABA binding sites also remained unaltered with aging in cortical membranes from Wistar rats. Moreover, the pattern and proportion of the [3H]flunitrazepam photoaffinity labeled peptides were also unmodified by aging. These results demonstrate the absence of modifications in Type I or total benzodiazepine binding sites of the GABAA receptor complex from adult and aged cortical membranes in Fischer or Wistar rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Affinity Labels
  • Aging / metabolism*
  • Animals
  • Anti-Anxiety Agents / pharmacokinetics
  • Binding, Competitive
  • Cerebral Cortex / metabolism*
  • Flunitrazepam / pharmacokinetics
  • Hypnotics and Sedatives / pharmacokinetics
  • In Vitro Techniques
  • Male
  • Membrane Proteins / metabolism
  • Muscimol / pharmacokinetics
  • Photochemistry
  • Pyridazines / pharmacokinetics
  • Pyridines / pharmacokinetics
  • Rats
  • Rats, Inbred F344
  • Rats, Wistar
  • Receptors, GABA-A / metabolism*
  • Zolpidem

Substances

  • Affinity Labels
  • Anti-Anxiety Agents
  • Hypnotics and Sedatives
  • Membrane Proteins
  • Pyridazines
  • Pyridines
  • Receptors, GABA-A
  • Muscimol
  • Flunitrazepam
  • CL 218872
  • Zolpidem