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.
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.
Ruano
D
D
Departamento de Bioquímica, Bromatología, Facultad de Farmacia, Universidad de Sevilla, Spain.
Machado
A
A
Vitorica
J
J
D000345:Affinity Labels; D000375:Aging / Q000378:metabolism*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D005445:Flunitrazepam / Q000493:pharmacokinetics; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009118:Muscimol / Q000493:pharmacokinetics; D010777:Photochemistry; D011724:Pyridazines / Q000493:pharmacokinetics; D011725:Pyridines / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D000077334:Zolpidem
D000345:Affinity Labels; D014151:Anti-Anxiety Agents; D006993:Hypnotics and Sedatives; D008565:Membrane Proteins; D011724:Pyridazines; D011725:Pyridines; D011963:Receptors, GABA-A; D009118:Muscimol; D005445:Flunitrazepam; C021604:CL 218872; D000077334:Zolpidem