Involvement of TRPV1 and TDAG8 in Pruriception Associated with Noxious Acidosis

详细信息    查看全文

• 作者：Shing-Hong Lin¹ ; Martin Steinhoff² ; ³ ; ⁴ ; Akihiko Ikoma⁴ ; Yen-Ching Chang⁵ ; Yuan-Ren Cheng¹ ; ⁶ ; Ravi Chandra Kopparaju¹ ; ⁷ ; Satoshi Ishii⁸ ; Wei-Hsin Sun⁵ ; ^{weihsin@cc.ncu.edu.tw} ; Chih-Cheng Chen¹ ; ⁶ ; ⁷ ; ⁹ ; ^{chih@ibms.sinica.edu.tw}
• 关键词：ASIC ; acid-sensing ion channel ; CP48/80 ; compound 40/80 ; DRG ; dorsal root ganglion ; ET ; endothelin ; GPCR ; G-protein&ndash ; coupled receptor ; HEPES ; 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid ; HT ; hydroxytryptamine ; IB4 ; isolectin B4 ; IRES ; internal ribosome entry site ; MES ; 2-(N-morpholino)ethanesulfonic acid ; Mrgpr ; Mas-related G protein-coupled receptor ; NaV1.8 ; voltage-gated sodium channel 1.8 ; PBS ; phosphate-buffered saline
• 刊名：Journal of Investigative Dermatology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：137
• 期：1
• 页码：170-178
• 全文大小：1378 K
• 卷排序：137

文摘

Itch and pain are closely related but are distinct sensations. Intradermal injection of acid generates pain in both rodents and humans; however, few studies have addressed the intriguing question of whether acid (protons) can evoke itch like other algogens by spatial contrast activation of single nociceptors. Here, we report that (i) citric acid (0.2 mol/L) pH-dependently induced a scratching response in mice when applied intradermally to nape or cheek skin, (ii) acidified buffer elevated intracellular calcium levels in dorsal root ganglion pruriceptors, and (iii) injection of intradermal citric acid (pH 3.0) into the nape induced a pruritogen-like but not algogen-like c-Fos immunoreactivity pattern in the cervical spinal cord. Using pharmacological and genetic approaches, we identified potential acid-sensing channels/receptors involved in acidic citrate-evoked itch. Results indicate that TRPV1, but neither ASIC3 nor TRPA1, is involved in the acidic citrate-induced scratching response. Furthermore, one of the proton-sensing G-protein–coupled receptors, TDAG8, was highly (∼71%) expressed in Nppb+ dorsal root ganglion pruriceptors. Itch induced by acidic citrate, but not α-methyl-5-hydroxytryptamine, chloroquine, compound 48/80, or bile acid, was markedly decreased in TDAG8–/– mice. In a heterologous expression system, TDAG8 potentiated the acid-induced calcium response by regulating TRPV1. Thus, protons could evoke pruriception by acting on TDAG8 to regulate TRPV1 activation with its mechanism of future therapeutic relevance.