Age-related modifications on the GABAA receptor binding properties from Wistar rat prefrontal cortex.
In the present communication we have investigated the pharmacological properties of the GABAA receptor from adult (3 months old) and aged (24 months old) Wistar rat prefrontal cortex. The prefrontal cortex is implicated in cognitive functions and stress and both processes seem to be altered during aging. These changes could be mediated by modifications in the GABAA receptor properties. Our results indicated the absence of generalized age-related modifications on the pharmacological properties of the GABAA receptor from prefrontal cortical membranes. Saturation experiments using the non-selective benzodiazepine [3H]flunitrazepam revealed that neither the Kd values or the Bmax were modified during aging. Moreover, Cl 218 872 displacement of [3H]flunitrazepam showed no age-related modifications on either the Kis or the relative proportion between the Type I and Type II benzodiazepine binding sites. Therefore, the benzodiazepine binding sites are well preserved in aged prefrontal cortex. On the other hand, saturation experiments using the GABA agonist [3H]muscimol demonstrated in the Bmax of the low affinity [3H]muscimol binding sites in aged rats (4.3 +/- 0.8 pmol/mg protein vs. 2.3 +/- 0.2 pmol/mg protein in adult and aged rats, respectively). However, no age-dependent modifications were observed in the allosteric interaction between GABA and benzodiazepine binding sites. These results demonstrate that the benzodiazepine binding sites and the GABA binding sites of the GABAA receptor complex from rat prefrontal cortical membranes are differentially affected by the aging process.
Ruano
D
D
Departamento de Bioquímica, Bromatología y Toxicología, Facultad de Farmacia, Universidad de Sevilla, Spain.
Araujo
F
F
Bentareha
R
R
Vitorica
J
J
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism; D001665:Binding Sites; D005445:Flunitrazepam / Q000378:metabolism; D018755:GABA Agonists / Q000378:metabolism; D018757:GABA Modulators / Q000378:metabolism; D008297:Male; D009118:Muscimol / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018755:GABA Agonists; D018757:GABA Modulators; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam