VOLTAGE CLAMP ELECTROPHYSIOLOGY SCREENING OF SELECTED COMPOUNDS FROM Zizyphus mauritiana AND Myristica fragrans ON SPECIFIC GABA RECEPTORS

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Date
2012-05
Authors
AHMAD TARMIZI, CHE HAS
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Publisher
Pusat Pengajian Sains Perubatan Universiti Sains Malaysia
Abstract
This study focused on the effects of the methanol crude extract of Zizyphus mauritiana leaves and the essential oil of the mesocarp of Myristica fragrans on the function of GABA (A) receptors. Both crude and essential oil were tested on the Xenopus laevis oocytes that comprised of GABA (A) receptors α1β2γ2s subtype. An automated fast perfusion system that applied the two microelectrodes voltage clamp measurement technique at EC5-10 of GABA was used. GABA or gammaaminobutyric acid is the major inhibitory neurotransmitter in the mammalian central nervous system and involves in the balance between excitation and inhibition in the neuronal cells. GABA expresses the inhibition actions by activation of the GABA receptors. These receptors can be divided into GABA (A), GABA (B) and GABA (C) receptors. GABA (A) receptors are pentameric protein inhibitory receptors that are arranged in a circle to form an intrinsic anion channel permeable to Cl- ions in the middle. These ion channels remain close until opened by specific agonist, GABA and modulated by a variety of compounds that act at its binding sites. The development of new ligands that which has the ability to bind on the GABA (A) receptors binding sites are the primary targets in current therapeutic study. There are many natural substances that have been identified to show potential in GABA (A) receptors activation thus influencing the functions of these ionotropic GABA (A) receptors. When tested at 100 μL/mL the essential oil enhanced I GABA by about 100%, however, the crude of Zizyphus mauritiana leaves at 100 μg/mL showed no statistical significance effect of I GABA. In the second assay, three synthetic compounds found in the essential oil; limonene, α-terpineol and myristicin and the fractions of Zizyphus mauritiana leaves extract were tested on GABA (A) receptors at GABA concentration eliciting 5-10% of the maximal response. α-Terpineol was the most potent and most efficient compound because it modulated the highest enhancement of I GABA by 229.6 ± 23.8% and the maximum current stimulation was 326.3 ± 43.8% at 500 μM with the EC50 value ≈ 88 μM. Myristicin also exhibited statistical significance of potentiation at 500 μM with 237.6 ± 35.1% enhancement of I GABA.
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Keywords
Neuroelectrophysiology
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