Changes in the characteristics of low affinity GABA binding sites elicited by Ro15-1788.
3H-GABA binding was studied in cortical membranes from cerebral cortex of handling-habituated and naive rats after the in vitro addition of Ro15-1788. At low concentrations (10(-8), 10(-9) M) Ro15-1788 increased the total number of low affinity 3H-GABA binding sites in brain tissue from naive rats but failed to modify 3H-GABA binding in tissue from handling-habituated ones. On the contrary, Ro15-1788 at higher concentrations (10(-5), 10(-6)M) decreased the total number of low affinity 3H-GABA binding sites in tissue from handling-habituated rats but failed to modify 3H-GABA binding in tissue from naive animals. Ro15-1788 (10(-7)M) failed to modify significantly low affinity 3H-GABA binding in membranes from both naive and handling-habituated rats. However, this concentration abolished the effect of beta-carbolines and diazepam on 3H-GABA binding in membranes from naive and handling-habituated rats, respectively. The changes in the affinity of 3H-GABA binding were inversely related to the changes in the number. The results suggest that: a) the action "in vitro" of Ro15-1788 on low affinity 3H-GABA binding depends from its concentration at the benzodiazepine recognition sites; b) the benzodiazepine recognition site has a modulatory role in the control of the function of GABA-ergic receptor. Our data might explain the conflicting results obtained with this compound "in vivo".
Concas
A
A
Serra
M
M
Crisponi
G
G
Nurchi
V
V
Corda
M G
MG
Biggio
G
G
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D005442:Flumazenil; D006234:Handling, Psychological; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001570:Benzodiazepinones; D002243:Carbolines; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D003975:Diazepam