Potentiation of the Ionotropic GABA Receptor Response by Whiskey Fragrance

• Published in: Journal of agricultural and food chemistry Vol. 50; no. 23; pp. 6828 - 6834
• Main Authors: Hossain, Sheikh Julfikar, Aoshima, Hitoshi, Koda, Hirofumi, Kiso, Yoshinobu
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 06.11.2002
• Subjects: Alcoholic Beverages; Animals; Brain Chemistry; Cattle; Drug Synergism; Female; GABA Antagonists; Gene Expression; Lactones - pharmacology; Male; Odorants; Oocytes - metabolism; Pentylenetetrazole; Phenols - pharmacology; Phenylpropionates - pharmacology; Rats; Rats, Wistar; Receptors, GABA-A - drug effects; Receptors, GABA-A - genetics; Receptors, GABA-A - physiology; Seizures - chemically induced; Transfection; Xenopus; Xenopus laevis
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf020448e

It is well-known that the target of most mood-defining compounds is an ionotropic γ-aminobutyric acid receptor (GABAA receptor). The potentiation of the response of these inhibitory neurotransmitter receptors induces anxiolytic, sedative, and anesthetic activity in the human brain. To study the effects of whiskey fragrance on the GABAA receptor-mediated response, GABAA receptors were expressed in Xenopus oocyte by injecting rat whole brain mRNA or cRNA prepared from the cloned cDNA for the α1 and β1 subunits of the bovine receptors. Most whiskey components such as phenol, ethoxy, and lactone derivatives potentiated the electrical responses of GABAA receptors, especially ethyl phenylpropanoate (EPP), which strongly potentiated the response. When this compound was applied to mice through respiration, the convulsions induced by pentetrazole were delayed, suggesting that EPP was absorbed by the brain, where it could potentiate the GABAA receptor responses. The extract of other alcoholic drinks such as wine, sake, brandy, and shochu also potentiated the responses to varying degrees. Although these fragrant components are present in alcoholic drinks at low concentrations (extremely small quantities compared with ethanol), they may also modulate the mood or consciousness of the human through the potentiation of the GABAA receptor response after absorption into the brain, because these hydrophobic fragrant compounds are easily absorbed into the brain through the blood−brain barrier and are several thousands times as potent as ethanol in the potentiation of the GABAA receptor-mediated response. Keywords: Ethyl phenylpropanoate; GABAA receptor; potentiation; whiskey fragrance; Xenopus oocyte