Temperature dependence of the benzodiazepine-receptor interaction.
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.
D000818:Animals; D001921:Brain / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008566:Membranes / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism*; D011963:Receptors, GABA-A; D013696:Temperature; D013816:Thermodynamics
D011955:Receptors, Drug; D011963:Receptors, GABA-A; D005445:Flunitrazepam; D003975:Diazepam