University of the Pacific
An electrophysiological study of the effects of resveratrol and catechin at GABAa receptors
Abstract
dc:description.abstract<p>Resveratrol and catechin have behavioral and neuroprotective effects that may be due to their interaction with neuronal ion channels. It was hypothesized that the grape compounds, resveratrol and catechin modulate GABAA<sub>A</sub> receptors. To address this hypothesis, the effects of resveratrol and catechin were investigated on human recombinant GABA<sub>A</sub> receptors expressed in HEK-293 cells using electrophysiological techniques.<.p><p>HEK-293 cells were cultured and transfected using eDNA encoding human GABA<sub>A</sub> receptors. GABA-evoked currents were recorded from HEK cells 24-48 hours following transfection. Cells were voltage clamped in the whole cell configuration at -60mV using the patch-clamp technique. Ligand-activated currents were recorded and stored, using Win WCP software, on a desktop computer.</p><p>Resveratrol (1- 100μM) dose-dependently potentiated GABA-evoked currents recorded from α<sub>1</sub>β<sub>2< /sup>γ<sub>2</sub> and α<sub>1</sub>β<sub>2</sub> GABA<sub>A</sub> receptors. Resveratrol did not modulate a α<sub>1</sub>β<sub>2< /sup>γ<sub>2</sub> and α<sub>1</sub>β<sub>2</sub> GABA<sub>A</sub> receptors. Furthermore, resveratrol did not act through the benzodiazepine binding site. The low efficacy and subunit selectivity of resveratrol is a promising discovery for the development of a highly specific GABAergic modulator. Conversely, catechin (1-100αM) dose-dependently inhibited GABA-evoked currents recorded from α<sub>1</sub>β<sub>2 and α<sup>1</sup>β<sub>1</sup> GABA<sub>A</sub> receptors. The degree of inhibition was the same for both receptor subtypes. Catechin did not modulate α<sub>1</sub>β<sub>2</sup>γ<sub>2</sub> or α<sub>1</sub>β<sub>1</sup>γ<sub>2</sub> GABA<sub>A</sub> receptors. The selectivity of catechin for receptors lacking the γ subunit is similar to the effects of zinc and did not involve the benzodiazephine site on GABA<sub>A</sub> receptors.</p><p>This study has shown that catechin and resveratrol are subunit-selective modulators of human GABA<sub>A</sub> receptors. These compounds could lead to the development of novel agents to be used in treating neurological disorders. These data support the use and study of natural products for the development of agents that act selectively on the nervous system.</p>
Degree
thesis:*- Name thesis:degree_name
- Master of Science (M.S.)
- Level thesis:degree_level
- Thesis - Pacific Access Restricted
- Discipline thesis:degree_discipline
- Pharmaceutical and Chemical Sciences
- Year dc:date.available
- 2007
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Harr, Jennifer C.
- Contributors dc:contributor
-
- Robert P. Halliwell
Subjects
dc:subject × 4Rights
dc:rightsIdentifiers
dc:identifier.*- Repository record dc:identifier
- https://scholarlycommons.pacific.edu/uop_etds/649
- OAI identifier oai:identifier
- oai:scholarlycommons.pacific.edu:uop_etds-1648