Ian C. Forster
Functional pharmacology of GABAA receptors containing the chicken brain γ4 subunit
Forster, Ian C.; Harvey, Robert J.; Darlison, Mark G.; Benson, Jack A.
Authors
Robert J. Harvey
Mark G. Darlison
Jack A. Benson
Abstract
The functional pharmacology of receptors composed of the chicken brain {GABAA} receptor γ4 subunit and the mammalian {GABAA} receptor α3 and β2 subunits was studied by heterologous expression in Xenopus laevis oocytes using the two electrode voltage-clamp technique. GABA-evoked currents had an {EC50} of 180±30 μM. Responses were blocked by the competitive and non-competitive {GABAA} receptor antagonists, bicuculline methochloride and picrotoxin. Sodium pentobarbital reversibly potentiated the current several-fold, and Zn2+ ions blocked the current with high potency (IC50=20 μM). GABA-evoked currents were potentiated by the benzodiazepine site full agonists flunitrazepam and triazolam and less by the partial agonists abecarnil and bretazenil. The inverse agonists methyl-β-carboline-3-carboxylate (β-CCM) and methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM) reduced the current. However, the imidazobenzodiazepine Ro 15-4513, which acts as an inverse agonist at mammalian αxβyγ2 {GABAA} receptors (where x=1, 2, 3 or 5, and y=1, 2 or 3), acted as a positive agonist at the γ4 subunit-containing receptors.
Citation
Forster, I. C., Harvey, R. J., Darlison, M. G., & Benson, J. A. (2001). Functional pharmacology of GABAA receptors containing the chicken brain γ4 subunit. European Journal of Pharmacology, 419(1), 1-7. https://doi.org/10.1016/S0014-2999%2801%2900964-5
| Journal Article Type | Article |
|---|---|
| Acceptance Date | Apr 3, 2001 |
| Online Publication Date | Jul 11, 2001 |
| Publication Date | 2001-05 |
| Deposit Date | Jul 26, 2016 |
| Journal | European Journal of Pharmacology |
| Print ISSN | 0014-2999 |
| Publisher | Elsevier |
| Peer Reviewed | Peer Reviewed |
| Volume | 419 |
| Issue | 1 |
| Pages | 1-7 |
| DOI | https://doi.org/10.1016/S0014-2999%2801%2900964-5 |
| Keywords | Benzodiazepine pharmacology, Electrophysiology, GABAA receptor, Xenopus oocyte, Zn2+ inhibition, |
| Public URL | http://researchrepository.napier.ac.uk/Output/316427 |