Benzodiazepine receptor and thyroid hormones: in vivo and in vitro modulation.
In rats rendered hyperthyroid by chronic treatment with L-triiodothyronine (T3) hormone there was a 21 and 27% decrease, respectively, in the number of binding sites for [3H]flunitrazepam ([3H]FNZ) and [3H]ethyl-beta-carboline-3-carboxylate ([3H]beta-CCE) without changes in affinity for the two ligands. Two weeks after thyroidectomy there was a 44% increase in [3H]FNZ sites and a 17% increase in [3H]beta-CCE binding sites. In vitro we found that T3 produces a decrease in Bmax and an increase in KD, both changes being characteristic of a mixed type of inhibition. Thyroid status dramatically affected the Ki of T3 in displacing [3H]FNZ from sites on isolated membranes of the cerebral cortex: in hypothyroid rats the Ki value was 0.9 microM, whereas in hyperthyroid rats, it was 83 microM, a 92-fold difference. In control rats, the Ki was 11 microM. These findings are discussed in relation to a possible modulation of benzodiazepine receptors by thyroid hormones.
Medina
J H
JH
De Robertis
E
E
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D006980:Hyperthyroidism / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D008297:Male; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013963:Thyroid Hormones / Q000494:pharmacology; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D011963:Receptors, GABA-A; D013963:Thyroid Hormones; D014284:Triiodothyronine; D005445:Flunitrazepam; D013974:Thyroxine