TY - JOUR T1 - Temperature dependence of the benzodiazepine-receptor interaction. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 20 LP - 25 VL - 22 IS - 1 AU - U Quast AU - H Mählmann AU - K O Vollmer Y1 - 1982/07/01 UR - http://molpharm.aspetjournals.org/content/22/1/20.abstract N2 - The temperature dependence of the interaction of three benzodiazepines with their receptors in rat brain membranes containing about 2 microM (endogenous) gamma-aminobutyric acid was investigated. van't Hoff plots of the equilibrium dissociation constants were linear for [3H]diazepam and its N-desmethyl derivative (N-desmethyldiazepam, NDz), whereas for [3H]flunitrazepam a break between two linear portions occurred at about 10 degrees. Binding of diazepam, NDz, and flunitrazepam (for the latter, at temperature greater than 10 degrees) is enthalpy-driven (delta H approximately -40 to -50 kJ/mole with a negligible contribution from delta S. The latter result indicates that the interaction is not a simple hydrophobic association, but that it may be more complex in nature, possibly involving a conformational transition of the receptor-ligand complex. The activation energy for dissociation of the [3H]flunitrazepam- and [3H]diazepam-receptor complexes is about 100 kJ/mole. Consequently, the complexes dissociate about 100 times faster on changing temperature from 0 degrees to 37 degrees. ER -