Kinetic differences between type I and type II benzodiazepine receptors

RR Trifiletti, MM Lo and SH Snyder

The kinetic properties of [3H]flunitrazepam [( 3H]FNZ) binding to central benzodiazepine receptors of bovine brain membranes at 0 degrees have been studied. Both dissociation and association (under pseudo- first order conditions) kinetics are biphasic, enabling definition of "fast" and "slow" compartments for both processes. In four brain regions examined, the proportion of receptor in the rapidly associating and rapidly dissociating compartments correlates with the proportion of Type I benzodiazepine receptor as determined from equilibrium radioligand binding studies in the four brain regions examined. Preincubation with the Type I-selective drugs CL-218,872 or methyl-beta- carboline-3-carboxylate (Ro 22-7497) reduces the size of the fast but not the slow kinetic compartments. Potencies of the drugs in eliciting these alterations in [3H]FNZ kinetics correlate with their potencies in displacing [3H]FNZ from Type I benzodiazepine receptors. Thus, in membrane preparations the more rapidly associating and dissociating site appears to represent the pharmacologically defined Type I benzodiazepine receptor, whereas the Type II receptors display slower association and dissociation kinetics. Soluble Type I receptors also display more rapid dissociation and association kinetics than soluble Type II receptors.

Volume 26, Issue 2, pp. 228-240, 09/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics