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TRP離子通道於致癢之角色

TRP Channels in the Pathophysiology of Itch

摘要


癢感(itch or pruritus)是一種令人不適,並誘發搔抓(scratching)反應的感覺,許多疾病都有癢的表現,例如異位性皮膚炎、乾癬、肝臟疾患,及尿毒症搔癢等等。急性癢感是人體的一種生理防禦機制,藉由移除或避開有害刺激,可以減少後續受到的傷害,但許多研究顯示慢性癢為神經免疫系統的病理性變化造成,會危害健康並降低病人的生活品質。TRP離子通道(transient receptor potential channels)為感官相關之重要分子家族,在哺乳類動物中已發現28種TRP離子通道,並為2021年諾貝爾獎的主題之一。許多證據顯示TRP離子通道(transient receptor potential channels)在癢覺及痛覺的傳遞佔有重要的角色。除此之外,TRP離子通道也擁有感知外在溫度、化學物質、滲透壓等變化的功能。在這些發現下,作用於TRP離子通道的藥物與化合物應運而生。本文將整理並介紹關於TRP離子通道的發現歷史、於癢覺的角色及新型TRP離子通道標的藥物的發展。

並列摘要


Itch (also known as pruritus) is an unpleasant sensation that elicits the desire or reflex of scratching. It is also an important manifestation of many diseases, including atopic dermatitis, psoriasis, hepatic diseases, and uremic pruritus. While acute itch is a protective mechanism to remove surface irritants to avoid further damage to the living organisms, chronic itch is a pathological phenomenon which poses detrimental effects on our health and significantly impacts the quality of life. TRP (transient receptor potential) channel superfamily consists of 28 individual channels in mammalians. Mounting evidences show that TRP channels play important roles in itch and pain signaling. They are also responsive to changes of external temperature, chemical stimuli, and osmolality. Multiple molecules and pharmaceutical agents were identified targeting TRP channels in order to develop antipruritic drugs. In this mini-review article we will introduce a brief history of the TRP channels, the roles of specific TRP channels in itch, and novel compounds targeting TRP channels with both antipruritic and antinociceptive properties.

參考文獻


Shim WS, Tak MH, Lee MH, et al. TRPV1 mediates histamine-induced itching via the activation of phospholipase A2 and 12-lipoxygenase. J Neurosci 2007;27:2331-7. https://doi.org/10.1523/JNEUROSCI.4643-06.2007
Liu Q, Tang Z, Surdenikova L, et al. Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus. Cell 2009;139:1353-65. https://doi.org/10.1016/j.cell.2009.11.034
Mela M, Mancuso A, Burroughs AK. Review article: pruritus in cholestatic and other liver diseases. Aliment Pharmacol Ther 2003;17:857-70. https://doi.org/10.1046/j.1365-2036.2003.01458.x
Lieu T, Jayaweera G, Zhao P, et al. The bile acid receptor TGR5 activates the TRPA1 channel to induce itch in mice. Gastroenterology 2014;147:1417-28. https://doi.org/10.1053/j.gastro.2014.08.042
Wilson SR, Thé L, Batia LM, et al. The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch. Cell 2013;155:285-95. https://doi.org/10.1016/j.cell.2013.08.057

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