Is stimulation of benzodiazepine receptor binding mediated by a novel GABA receptor?

Abstract

A STEREOSPECIFIC, saturable, high affinity binding site for ³H-diazepam has recently been characterised in membrane fractions isolated from the brains of mammals¹, including man², which has been suggested to represent the pharmacological benzodiazepine (BZ) receptor^2–4. Electrophysiological⁵ and biochemical⁶ results indicate that BZs exert their main actions in the central nervous system by facilitation of the synaptic action of γ-aminobutyric acid (GABA). Evidence for an interaction between GABA and BZs at the receptor level has recently been obtained^7–11. Thus, GABA has been shown to stimulate BZ binding^8–11 and there is preliminary evidence that this process is mediated by a specific GABA recognition site, as the GABA agonists muscimol⁸, imidazoleacetic acid¹¹, and 3-guanidino-propionic acid¹¹ also stimulate ³H-diazepam binding. We now report different structural requirements for stimulation of ³H-diazepam binding to rat brain synaptic membranes compared with those for inhibition of Na⁺-independent ³H-GABA binding¹². We suggest that stimulation by GABA of BZ receptor binding involves a novel type of a GABA receptor.