Article date: 1985/4/1
PubMed ID: 2983028
Journal name: Journal of neurochemistry (ISSN: 0022-3042)
GABAA receptor agonists modulate [3H]diazepam binding in rat cortical membranes with different efficacies. At 23 degrees C, the relative potencies for enhancement of [3H]diazepam binding by agonists parallel their potencies in inhibiting [3H]gamma-aminobutyric acid [( 3H]GABA) binding. The agonist concentrations needed for enhancement of [3H]diazepam binding are up to 35 times higher than for [3H]GABA binding and correspond closely to the concentrations required for displacement of [3H]bicuculline methochloride (BMC) binding. The maximum enhancement of [3H]diazepam varied among agonists: muscimol = GABA greater than isoguvacine greater than 3-aminopropane sulphonic acid (3APS) = imidazoleacetic acid (IAA) greater than 4,5,6,7-tetrahydroisoxazolo (4,5,6)-pyridin-3-ol (THIP) = taurine greater than piperidine 4-sulphonic acid (P4S). At 37 degrees C, the potencies of agonists remained unchanged, but isoguvacine, 3 APS, and THIP acquired efficacies similar to GABA, whereas IAA, taurine, and P4S maintained their partial agonist profiles. At both temperatures the agonist-induced enhancement of [3H]diazepam binding was reversible by bicuculline methobromide and by the steroid GABA antagonist RU 5135. These results stress the importance of studying receptor-receptor interaction under near-physiological conditions and offer an in vitro assay that may predict the agonist status of putative GABA receptor ligands.
Author List: Wong E H, Iversen L L
Publication Types: Comparative Study; Journal Article
Substances mentioned in the article: Androstanes; Azasteroids; GABA Antagonists; Imidazoles; Isonicotinic Acids; Isoxazoles; Piperidines; Receptors, GABA-A; Taurine; Muscimol; gamma-Aminobutyric Acid; tramiprosate; bicuculline methobromide; piperidine-4-sulfonic acid; imidazoleacetic acid; gaboxadol; Diazepam; RU 5135; Bicuculline; isoguvacine;
Mesh terms: Androstanes/pharmacology; Animals; Azasteroids/pharmacology; Bicuculline/analogs & derivatives; Cell Membrane/metabolism; Cerebral Cortex/metabolism; Diazepam/metabolism; GABA Antagonists; Imidazoles/pharmacology; Isonicotinic Acids/pharmacology; Isoxazoles/pharmacology; Muscimol/pharmacology; Piperidines/pharmacology; Rats; Receptors, GABA-A/drug effects; Taurine/analogs & derivatives; gamma-Aminobutyric Acid/analogs & derivatives;