Glucocorticoids are modulators of GABAA receptors in brain.
Modulation of binding of [3H]muscimol, a GABAA receptor agonist, by natural and synthetic glucocorticoids was investigated in crude synaptosomal membranes and in brain sections of rat. In adrenalectomized (Adx) rats, muscimol binding was reduced by 30-50% in cerebral cortex, cerebellum, thalamus and hippocampus, as compared to sham-operated controls. This decrease was due to reduced binding affinities of GABA receptors for muscimol. In contrast muscimol binding was increased by 38% in the hypothalamus and did not change in the pons-medulla after Adx. Nanomolar concentrations of corticosterone and pregnenolone-sulfate, but not dexamethasone, enhanced muscimol binding in brain regions that were characterized by reduced binding following Adx. This steroid-induced increase in muscimol binding was due to enhanced affinities of GABA receptors.
Majewska
M D
MD
Bisserbe
J C
JC
Eskay
R L
RL
D000315:Adrenalectomy; D000818:Animals; D001921:Brain / Q000502:physiology*; D003345:Corticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000502:physiology*; D009118:Muscimol / Q000378:metabolism; D011284:Pregnenolone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*
D005938:Glucocorticoids; D011963:Receptors, GABA-A; C018370:pregnenolone sulfate; D009118:Muscimol; D011284:Pregnenolone; D003907:Dexamethasone; D003345:Corticosterone