beta-Lumicolchicine interacts with the benzodiazepine binding site to potentiate GABAA receptor-mediated currents.
J Neurochem
; 62(5): 1790-4, 1994 May.
Article
em En
| MEDLINE
| ID: mdl-8158128
ABSTRACT
An analogue of colchicine, beta-lumicolchicine, does not bind tubulin or disrupt microtubules. However, this compound is not pharmacologically completely inactive. beta-Lumicolchicine was found to competitively inhibit [3H]flunitrazepam binding and to enhance muscimol-stimulated 36Cl- uptake in mouse cerebral cortical microsacs. It also markedly potentiated GABA responses in Xenopus oocytes expressing human alpha 1 beta 2 gamma 2S, but not alpha 1 beta 2, GABAA receptor subunits; this potentiation was reversed by the benzodiazepine receptor antagonist flumazenil. These results strongly suggest a direct effect of beta-lumicolchicine on the GABAA receptor/chloride channel complex and caution that it possesses pharmacological effects, despite its inability to disrupt microtubules. Furthermore, beta-lumicolchicine is structurally unrelated to benzodiazepines or quinolines and may provide a novel approach to the synthesis of ligands for this receptor.
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Base de dados:
MEDLINE
Assunto principal:
Córtex Cerebral
/
Receptores de GABA-A
/
Flunitrazepam
/
Ácido gama-Aminobutírico
/
Lumicolchicinas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
1994
Tipo de documento:
Article