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Modulation of [ 3 H]Diazepam Binding in Rat Cortical Membranes by GABA A Agonists
Author(s) -
Wong Erik H. F.,
Iversen Leslie L.
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb08739.x
Subject(s) - muscimol , bicuculline , agonist , diazepam , chemistry , gabaa receptor , partial agonist , gaba receptor antagonist , taurine , gaba receptor , pharmacology , receptor , endocrinology , biochemistry , biology , amino acid
GABA A receptor agonists modulate [ 3 H]diazepam binding in rat cortical membranes with different efficacies. At 23°C, the relative potencies for enhancement of [ 3 H]diazepam binding by agonists parallel their potencies in inhibiting [ 3 H]‐γ‐aminobutyric acid ([ 3 H]GABA) binding. The agonist concentrations needed for enhancement of [ 3 H]diazepam binding are up to 35 times higher than for [ 3 H]GABA binding and correspond closely to the concentrations required for displacement of [ 3 H]bicuculline methochloride (BMC) binding. The maximum enhancement of [ 3 H]diazepam varied among agonists: muscimol = GABA > isoguvacine > 3‐aminopropane sulphonic acid (3APS) = imidazoleacetic acid (IAA) > 4,5,6,7‐tetrahydroisoxazolo (4,5,6)‐pyridin‐3‐ol (THIP) = taurine > piperidine 4‐sulphonic acid (P4S). At 37°C, the potencies of agonists remained unchanged, but isoguvacine, 3APS, 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 [ 3 H]diazepam binding was reversible by bicuculline methobromide and by the steroid GABA antagonist RU 5135. These results stress the importance of studying receptor‐receptor in teraction under near‐physiological conditions and offer an in vitro assay that may predict the agonist status of putative GABA A receptor ligands.