Benzodiazepine receptors: multiple receptors or multiple conformations?

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Evidence suggests at least two central benzodiazepine receptor subtypes (BZ1 and BZ2).
• Benzodiazepine receptors are known to exist in multiple conformations.

Purpose of the Study:

• To investigate the subtypes and conformations of GABA-benzodiazepine receptors.
• To identify proteins associated with benzodiazepine receptor subtypes.
• To elucidate the structural basis for differing benzodiazepine drug effects.

Main Methods:

• Utilizing reversible and irreversible binding studies.
• Employing 3H-flunitrazepam as a photoaffinity label for benzodiazepine receptors.

Main Results:

• Identified P51 protein associated with the BZ1 receptor.
• Suggested BZ2 receptor may comprise multiple subtypes linked to distinct proteins.
• Indicated four distinct benzodiazepine binding sites within the GABA-benzodiazepine receptor complex.
• Supported the existence of multiple receptor conformations.

Conclusions:

• Hypothesized several GABA-benzodiazepine receptor subtypes, each with four binding sites and multiple conformations.
• This hypothesis reconciles existing experimental data.
• May partially explain differential clinical effects of structurally similar benzodiazepines.