TY - JOUR
T1 - γ-Aminobutyric acid- and benzodiazepine-binding sites in human anterior pituitary tissue
AU - Grandison, L.
AU - Cavagnini, F.
AU - Schmid, R.
AU - Invitti, S. C.
AU - Guidotti, A.
PY - 1982
Y1 - 1982
N2 - The existence of a γ-aminobutyric acid (GABA) system in human anterior pituitary tissue was examined. Crude membrane fractions prepared from human anterior pituitary tissue bound tritiated GABA. The binding was saturable, and Scatchard analysis indicated a single binding site of high affinity (K(d) = 40 nM)) and a maximum binding of 1.2 pmol/mg protein. Binding was displaced in a dose-related manner by the GABA agonists muscimol (K(I) = 1 x 10 -8 M), isoguvacine (K(I) = 6 x 10 -6 M), THIP (4,5,6,7-tetrahydroisoxazole-[5,4-c]pyridin-3-ol); K(I)) = 5 x 10 -7 M), and the antagonist (+)bicuculline (KI) = 5 x 10 -5 M) but not its inactive stereoisomer (-)bicucculline (K(I) > 10 -3 m). In anterior pituitary tissue, a significant concentration of GABA was found (mean 2.5 ± 0.5 nmol/mg protein) but no glutamic acid decarboxylase activity, the enzyme synthesizing GABA, was detected using a highly sensitive assay. In addition, benzodiazepine binding was present. An affinity of approximately 1.5 nM and a B(max) of approximately 0.75 pmol/mg protein were observed when using [ 3H]diazepam as the ligand. No saturable clonazepam binding occurred, and only slight GABA stimulation of diazepam binding was observed (mean, 18%; range, 6-38%). The ability of GABA and benzodiazepine to alter PRL secretion in rats suggests that the human pituitary GABA-binding sites decribed here might also mediate effects of PRL release.
AB - The existence of a γ-aminobutyric acid (GABA) system in human anterior pituitary tissue was examined. Crude membrane fractions prepared from human anterior pituitary tissue bound tritiated GABA. The binding was saturable, and Scatchard analysis indicated a single binding site of high affinity (K(d) = 40 nM)) and a maximum binding of 1.2 pmol/mg protein. Binding was displaced in a dose-related manner by the GABA agonists muscimol (K(I) = 1 x 10 -8 M), isoguvacine (K(I) = 6 x 10 -6 M), THIP (4,5,6,7-tetrahydroisoxazole-[5,4-c]pyridin-3-ol); K(I)) = 5 x 10 -7 M), and the antagonist (+)bicuculline (KI) = 5 x 10 -5 M) but not its inactive stereoisomer (-)bicucculline (K(I) > 10 -3 m). In anterior pituitary tissue, a significant concentration of GABA was found (mean 2.5 ± 0.5 nmol/mg protein) but no glutamic acid decarboxylase activity, the enzyme synthesizing GABA, was detected using a highly sensitive assay. In addition, benzodiazepine binding was present. An affinity of approximately 1.5 nM and a B(max) of approximately 0.75 pmol/mg protein were observed when using [ 3H]diazepam as the ligand. No saturable clonazepam binding occurred, and only slight GABA stimulation of diazepam binding was observed (mean, 18%; range, 6-38%). The ability of GABA and benzodiazepine to alter PRL secretion in rats suggests that the human pituitary GABA-binding sites decribed here might also mediate effects of PRL release.
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M3 - Article
C2 - 6276430
AN - SCOPUS:0020462540
VL - 54
SP - 597
EP - 601
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 3
ER -