Benzodiazepine receptors: Multiple receptors or multiple conformations?

Abstract

Several lines of evidence from reversible binding studies seem to indicate there are at least two “central” benzodiazepine receptor subtypes, the BZ₁ and BZ₂ receptors. Irreversible binding studies, using³H-flunitrazepam as a photoaffinity label for benzodiazepine receptors, not only are in perfect agreement with the data from reversible binding studies but extend these studies by identifying P₅₁, a protein with apparent molecular weight 51,000, as a protein associated with the BZ₁ receptor and by suggesting that the BZ₂ receptor might actually consist of several different benzodiazepine receptors associated with different and distinct proteins irreversibly labeled by³H-flunitrazepam. Other reversible binding studies have accumulated indicating the existence of several different conformations of benzodiazepine receptors. Irreversible binding studies support this conclusion and in addition suggest the existence of four different benzodiazepine binding sites within the GABA-benzodiazepine receptor complex. It is therefore hypothesized that there are several different GABA-benzodiazepine receptor subtypes all of which have four distinct benzodiazepine binding sites which can exist in at least three different but freely interconvertible conformations. This hypothesis can account for all experimental observations obtained so far and might partially explain the distinct clinical effects of structurally similar benzodiazepines.