Infinity Supercritical LLC


Publication Title | CBD Rich Hemp Oil

Cannabis Search Engine Series

Hops | Oil Extraction | Cultivation | Supercritical CO2 Fluid Extraction search was updated real-time via Filemaker on:

Hops | Oil Extraction | Cultivation | Supercritical CO2 Fluid Extraction | Return to Search List

Search Completed | Title | CBD Rich Hemp Oil
Original File Name Searched: J. Biol. Chem.-2014-Ohara-jbc.M114.600932.pdf | Google It | Yahoo | Bing



Page Number: 001
Previous Page View | Next Page View

Text | CBD Rich Hemp Oil | 001



JBC Papers in Press. Published on December 18, 2014 as Manuscript M114.600932 The latest version is at http://www.jbc.org/cgi/doi/10.1074/jbc.M114.600932

Hop derived sesquiterpene eudesmol activates human TRPA1

Identification of significant amino acids in multiple transmembrane domains of human transient receptor potential ankyrin 1 (TRPA1) for activation by eudesmol, an oxygenized sesquiterpene in hop essential oil*

2

Kazuaki Ohara1, Takafumi Fukuda1, Hiroyuki Okada1, Sayoko Kitao1, Yuko Ishida1, Kyoko Kato1, Chika Takahashi1, Mikio Katayama1, Kunitoshi Uchida2, and Makoto Tominaga2

1 Research Laboratories for Health Science and Food Technologies, Kirin Company, Limited. Yokohama, Kanagawa, 236-0004, Japan

Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institute of Natural Sciences, Okazaki, Aichi, 444-8787,

Japan

*Running title: Hop derived sesquiterpene eudesmol activates human TRPA1

To whom correspondence should be addressed: Kazuaki Ohara, Krin Company, Limited, Research Laboratories for Health Science and Food Technologies, 1-13-5, Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; Tel.:+81-45-330-9006; Fax.:+81-45-788-4047; e-mail: Kazuaki_Ohara@kirin.co.jp

Key words: calcium channel, mutagenesis, natural product, terpenoid, transient receptor potential channels (TRP channels)

Capsule

Background: Transient receptor potential ankyrin 1 (TRPA1) is activated by many spicy compounds by unknown mechanisms. Results: The amino acids critical for the activation of TRPA1 by the hop derived sesquiterpene β-eudesmol, were identified. Conclusion: Multiple transmembrane domains are crucial for β-eudesmol derived TRPA1 activation.

Significance: New insight for activation mechanism of TRPA1 is revealed by our study.

ABSTRACT

Transient receptor potential ankyrin

1 (TRPA1) is a calcium-permeable non-selective cation channel, which is activated by various noxious or irritant substances in nature, including spicy compounds. Many TRPA1 chemical activators have been reported, however, only limited information is available regarding the amino acid residues that contribute to the activation by non-electrophilic activators, while activation mechanisms by electrophilic ligands have been well characterized. We used intracellular Ca2+ measurements and whole-cell patch-clamp recordings to show that eudesmol, an oxygenated

sesquiterpene present at high concentrations in the essential oil of hop cultivar Haratau Hersbrucker, could activate human TRPA1. Gradual activation of inward currents with outward rectification by eudesmol was observed in human embryonic kidney-derived 293 cells expressing human TRPA1. This activation was completely blocked by a TRPA1-specific inhibitor, HC03-0031. We identified three critical amino acid residues in human TRPA1 in putative transmembrane domains 3, 4, and 5, namely serine at 813, tyrosine at 840, and serine at 873, for activation by β-eudesmol in a systematic mutational study. Our results revealed a new TRPA1 activator in hop essential oil, and provides a novel insight into mechanisms of human TRPA1 activation by non-electrophilic chemicals.

The transient receptor potential (TRP) channel family is known to be involved in detection of various noxious stimuli, such as thermal, chemical and mechanical stimulus (1). Among them, transient receptor potential ankyrin 1 (TRPA1) channel is a nonselective cation channel mainly expressed in primary sensory neurons (2). It responds to a wide variety of irritant sensory stimuli, including pungent ingredients of various

1

Copyright 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Downloaded from http://www.jbc.org/ by guest on August 18, 2016

Image | CBD Rich Hemp Oil



cbd-rich-hemp-oil
Supercritical CO2 Fluid Extractor | Oil Extract Using Infinity Supercritical CO2 Extraction System - Botanical CO2 Extraction System - Go to website

Search Engine Contact: greg@infinitysupercritical.com