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瞬时受体电位 A1 的激活由一种非刺激性辣椒素类似化合物,辣椒素引起。

Activation of transient receptor potential A1 by a non-pungent capsaicin-like compound, capsiate.

机构信息

Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki, Aichi, Japan.

出版信息

Br J Pharmacol. 2012 Mar;165(5):1476-86. doi: 10.1111/j.1476-5381.2011.01634.x.


DOI:10.1111/j.1476-5381.2011.01634.x
PMID:21883144
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3372731/
Abstract

BACKGROUND AND PURPOSE: Capsiate is produced by 'CH-19 Sweet' (Capsicum annuun L.), a non-pungent cultivar of red pepper. Like capsaicin, capsiate is thought to enhance energy metabolism by activating the sympathetic nervous system and suppressing inflammation, but the underlying mechanisms for this are uncertain. We previously reported that capsiate could activate transient receptor potential vanilloid 1 (TRPV1), a capsaicin receptor. The purpose of the present study is to investigate whether capsinoids activate other TRP channels. EXPERIMENTAL APPROACH: Using Ca(2+) imaging and whole-cell patch-clamp methods, we analysed the response of TRP channels to three kinds of capsinoids, capsiate, dihydrocapsiate and nordihydrocapsiate, in HEK293T cells expressing TRP channels or in primary cultures of mouse dorsal root ganglion neurons. KEY RESULTS: We found that in both cell types TRP ankyrin 1 (TRPA1) had a slightly weaker response to capsinoids compared with TRPV1, with the capsiate EC(50) for TRPA1 activation being more than that for TRPV1 activation, and that the capsinoid-evoked action was blocked by a specific TRPA1 antagonist. TRPA1 was activated by capsinoids, but not by their degradation products. Amino acids known to participate in TRPA1 activation following cysteine covalent modification or zinc treatment were not involved in the activation of TRPA1 by capsinoid. CONCLUSIONS AND IMPLICATIONS: Taken together, these results indicate that capsinoids activate TRPA1 by an as yet unknown mechanism, and TRPA1 could be involved in physiological phenomena associated with capsinoid treatment.

摘要

背景与目的:辣椒素是由“CH-19 甜椒”(Capsicum annuun L.)产生的,这是一种不辣的红辣椒品种。与辣椒素一样,辣椒素被认为通过激活交感神经系统和抑制炎症来增强能量代谢,但这种作用的潜在机制尚不清楚。我们之前报道过辣椒素可以激活瞬时受体电位香草醛 1(TRPV1),即辣椒素受体。本研究的目的是研究辣椒素是否能激活其他 TRP 通道。

实验方法:使用 Ca(2+)成像和全细胞膜片钳技术,我们分析了三种辣椒素(辣椒素、二氢辣椒素和去甲二氢辣椒素)在表达 TRP 通道的 HEK293T 细胞或小鼠背根神经节神经元原代培养物中对 TRP 通道的反应。

主要结果:我们发现,在这两种细胞类型中,TRP 锚蛋白 1(TRPA1)对辣椒素的反应略弱于 TRPV1,辣椒素激活 TRPA1 的 EC(50)大于激活 TRPV1 的 EC(50),并且辣椒素诱发的作用被特异性 TRPA1 拮抗剂阻断。辣椒素激活 TRPA1,但不激活其降解产物。参与半胱氨酸共价修饰或锌处理后 TRPA1 激活的氨基酸不参与辣椒素激活 TRPA1。

结论和意义:综上所述,这些结果表明,辣椒素通过未知的机制激活 TRPA1,TRPA1 可能参与与辣椒素治疗相关的生理现象。

相似文献

[1]
Activation of transient receptor potential A1 by a non-pungent capsaicin-like compound, capsiate.

Br J Pharmacol. 2012-3

[2]
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[6]
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[7]
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本文引用的文献

[1]
Guide to Receptors and Channels (GRAC), 5th edition.

Br J Pharmacol. 2011-11

[2]
Capsinoids, non-pungent capsaicin analogs, reduce body fat accumulation without weight rebound unlike dietary restriction in mice.

Biosci Biotechnol Biochem. 2011

[3]
Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes.

Br J Pharmacol. 2011-8

[4]
Effects of capsinoid ingestion on energy expenditure and lipid oxidation at rest and during exercise.

Nutr Metab (Lond). 2010-8-3

[5]
Assessment of the biological similarity of three capsaicin analogs (Capsinoids) found in non-pungent chili pepper (CH-19 Sweet) fruits.

Biosci Biotechnol Biochem. 2010

[6]
Capsiate inhibits ultraviolet B-induced skin inflammation by inhibiting Src family kinases and epidermal growth factor receptor signaling.

Free Radic Biol Med. 2010-2-1

[7]
Compounds from Sichuan and Melegueta peppers activate, covalently and non-covalently, TRPA1 and TRPV1 channels.

Br J Pharmacol. 2009-7-8

[8]
Zinc activates damage-sensing TRPA1 ion channels.

Nat Chem Biol. 2009-3

[9]
Effects of novel capsinoid treatment on fatness and energy metabolism in humans: possible pharmacogenetic implications.

Am J Clin Nutr. 2009-1

[10]
Thymol and related alkyl phenols activate the hTRPA1 channel.

Br J Pharmacol. 2008-4

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