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

R M Dawson; M Poretski

doi:10.1016/0306-3623(89)90341-8

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

Gen Pharmacol. 1989;20(6):843-8. doi: 10.1016/0306-3623(89)90341-8.

Authors

R M Dawson¹, M Poretski

Affiliation

¹ Materials Research Laboratory, Defence Science and Technology Organisation, Ascot Vale, Vic, Australia.

PMID: 2556320
DOI: 10.1016/0306-3623(89)90341-8

Abstract

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.

MeSH terms

Animals
Benzodiazepines / pharmacology
Brain Chemistry / drug effects
Guinea Pigs
Hippocampus / drug effects
Hippocampus / metabolism*
In Vitro Techniques
Kinetics
Ligands
Receptors, GABA-A / drug effects
Receptors, GABA-A / metabolism*
Temperature
gamma-Aminobutyric Acid / metabolism*

Substances

Ligands
Receptors, GABA-A
Benzodiazepines
gamma-Aminobutyric Acid