Endogenous ligands of the benzodiazepine receptor.
The benzodiazepine receptor (BZR) is a site on the GABAA-receptor-chloride channel by means of which benzodiazepine and nonbenzodiazepine compounds produce positive or negative allosteric modulation of the channel gating function and which is blocked by BZR antagonists. Whether the BZR is acted upon by one or several endogenous ligands under normal or pathologic conditions is still a controversial issue after 10 years of intensive research. Evidence is provided for the unconventional view that there need not be an endogenous ligand of the BZR; neither to justify the existence of this receptor, nor to explain the effects of exogenous BZR ligands. Out of a number of putative endogenous compounds with affinity for the BZR, the peptide DBI (diazepam binding inhibitor) stands out as a ligand that might act on the BZR in a subset of GABAergic synapses or under particular situations. The low affinity of DBI for the BZR and its distribution in the body suggest, however, that its primary function might not be at the level of the BZR.
Haefely
W
W
Pharmaceutical Research Department, F. Hoffmann-La Roche & Co., Ltd., Basel, Switzerland.
D000818:Animals; D001569:Benzodiazepines / Q000032:analysis; D001923:Brain Chemistry; D026261:Diazepam Binding Inhibitor; D006801:Humans; D008024:Ligands; D009479:Neuropeptides / Q000032:analysis*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D026261:Diazepam Binding Inhibitor; D008024:Ligands; D009479:Neuropeptides; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid