Date of Award

3-2015

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Medical Education

First Advisor

Prof. Murat Oz

Second Advisor

Chris Howarth

Third Advisor

Neil S Millar

Abstract

Plants and phytochemicals have been used for centuries for therapeutic purposes. Essential oils from these plants are complex mixtures and may possess a large spectrum of biological activities many of them of clinical interest. Among the active constituents of essential oils, monoterpenes, demonstrated valuable antioxidant, antiviral, antimicrobial, anticancer, analgesic and anti-inflammatory effects. In recent years, actions of monoterpenes on the function of ion channels have been investigated. In the present study, effects of different monoterpenes including carvacrol, carveol, d-carvone, eugenol, (+)-pulegone, thymol, thymoquinone, menthome and limonene, on the function of the cloned α7 subunit of human nicotinic acetylcholine (nACh) receptor expressed in Xenopus oocytes were investigated by using the two-electrode voltage-clamp technique. All monoterpenes caused a variable extent of reversible inhibition of Ach (100 μM)-induced currents except vanillin and d-carvone. Carveol showed maximum potency of inhibition with an IC50 value of 8.3 μM. The effect of carveol was further investigated and found to be independent of the membrane potential. Carveol (10 μM) did not affect the activity of endogenous Ca2+-dependent Cl- channels since the extent of inhibition by carveol was unaltered by the intracellularly injected Ca2+ chelator BARTA and profusion with Ca2+-free bathing solution containing 2 mM Ba2+. The effect of carveol was associated with decrease potency of the Ach, and the inhibition was fully reversed by increasing ACh concentrations, suggesting that this drug acts in a competitive manner. In conclusion, these results demonstrated for the first time that monoterpenes inhibit directly the function of human α7-nACh receptors expressed in Xenopus oocytes. It appears that the extent of inhibition by monoterpenes differs significantly depending on their chemical structures.

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