| Autor: |
Mihic SJ; Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262., Whatley VJ, McQuilkin SJ, Harris RA |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of neurochemistry [J Neurochem] 1994 May; Vol. 62 (5), pp. 1790-4. |
| DOI: |
10.1046/j.1471-4159.1994.62051790.x |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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