Inhibition constants and GABA-shifts at 2 degrees C and 37 degrees C for a spectrum of ligands acting on the benzodiazepine receptors of guinea pig hippocampus.
1. Dissociation constants and Hill coefficients were determined for 13 ligands inhibiting the binding of [3H]flunitrazepam to the benzodiazepine receptors of guinea pig hippocampus at 2 degrees C and 37 degrees C. 2. The ratio of I50 in the absence of gamma-aminobutyric acid (GABA) to that in the presence of 10(-5) M GABA (the GABA-shift) was found to vary from 0.4 to 2.5. 3. There was no correlation between the pharmacological activity of the ligand and the GABA-shift, or between the pharmacological activity and the magnitude of the increase in affinity of the ligand for the receptor as the temperature decreased from 37 degrees C to 2 degrees C. 4. A correlation was observed between the temperature-induced affinity change and the GABA-shift at 37 degrees C.
Dawson
R M
RM
Materials Research Laboratory, Defence Science and Technology Organisation, Ascot Vale, Vic, Australia.
Poretski
M
M
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013696:Temperature; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D008024:Ligands; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid