Molecular Pharmacology, Vol 20, 16-21, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Studies on the Relationship of -Aminobutyric Acid-Stimulated Diazepam Binding and the -Aminobutyric Acid Receptor

¹ Clinical Psychobiology Branch, National Institute of Mental Health, Bethesda, Maryland 20205

The three binding parameters [³H]muscimol binding, [³H]diazepam binding, and -aminobutyric acid (GABA)-stimulated [³H]diazepam binding are compared in various brain areas and in response to various protein and membrane modifying reagents. Comparison of rat forebrain and cerebellum revealed a much higher ratio of [³H]muscimol- to [³H]diazepam-binding sites in cerebellum and less GABA-stimulated [³H]diazepam binding. Both sulfhydryl reducing and alkylating agents reduced [³H]muscimol binding (decreased binding affinity), and increased GABA-stimulated [³H]diazepam binding. Triton X-100-treated membranes display an increase in both the number and affinity of [³H]muscimol-binding sites, no change in basal [³H]diazepam binding, and a decrease in GABA-stimulated [³H]diazepam binding. The observed relationship between [³H]-muscimol-binding sites and the degree of GABA-stimulated [³H]diazepam binding suggests that the high affinity muscimol-binding site is not mediating the GABA enhancement effect.