title: Modulation of [3H]diazepam binding in rat cortical membranes by GABAA agonists.
abstract: 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.
authors.forename: E H
authors.initials: EH
authors.lastname: Wong
authors.forename: L L
authors.initials: LL
authors.lastname: Iversen
mesh_terms: D000731:Androstanes / Q000494:pharmacology; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D003975:Diazepam / Q000378:metabolism*; D018756:GABA Antagonists; D007093:Imidazoles / Q000494:pharmacology; D007539:Isonicotinic Acids / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000731:Androstanes; D001378:Azasteroids; D018756:GABA Antagonists; D007093:Imidazoles; D007539:Isonicotinic Acids; D007555:Isoxazoles; D010880:Piperidines; D011963:Receptors, GABA-A; D013654:Taurine; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; C001355:tramiprosate; C036615:bicuculline methobromide; C023402:piperidine-4-sulfonic acid; C005954:imidazoleacetic acid; C015542:gaboxadol; D003975:Diazepam; C032061:RU 5135; D001640:Bicuculline; C015300:isoguvacine