Effects of thyroxine and its related compounds on cerebral GABA receptors: inhibitory action on benzodiazepine recognition site in GABAA receptor complex.
The effects of thyroxine and its related derivatives on gamma-aminobutyric acid (GABA) receptors in the rat brain were examined. D-Thyroxine strongly inhibited [3H]flunitrazepam binding to benzodiazepine receptor in crude synaptic membrane from the rat brain. The Scatchard analysis of the [3H]flunitrazepam binding in the presence of D-thyroxine indicated the decreases in the affinity and maximum number of binding site. Furthermore, D-thyroxine inhibited the enhancing effect of flunitrazepam on GABA-stimulated 36Cl- influx into membrane vesicles, although GABA-stimulated 36Cl- influx alone was not affected by D-thyroxine. On the other hand, the effects of thyroxine and its related derivatives on cerebral GABAB receptor binding were not noted. These results suggest that D-thyroxine may be a drug which is able to modulate the function of GABAA receptor complex via the inhibitory action on benzodiazepine recognition site.
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
R
R
Narihara
M
M
Hirouchi
T
T
Ichida
K
K
Kuriyama
E
E
Roberts
D000818:Animals; D001569:Benzodiazepines / Q000737:chemistry; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D003918:Dextrothyroxine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D010134:Fenclonine / Q000494:pharmacology; D005445:Flunitrazepam / Q000037:antagonists & inhibitors*; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D066298:In Vitro Techniques; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000737:chemistry; D018080:Receptors, GABA-B / Q000737:chemistry; D013570:Synaptic Membranes / Q000378:metabolism; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
D002712:Chlorides; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D014284:Triiodothyronine; D001569:Benzodiazepines; D003918:Dextrothyroxine; D005445:Flunitrazepam; D013974:Thyroxine; D010134:Fenclonine