Tris-hydroxymethyl-aminomethane enhances capsaicin-induced intracellular Ca²⁺ influx through transient receptor potential V1 (TRPV1) channels

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• 作者：Satoshi Murakami^a ; Yuka Sudo^b ; ^c ; Kanako Miyano^c ; Hitomi Nishimura^b ; ^c ; Motohiro Matoba^d ; ^e ; Seiji Shiraishi^c ; ^f ; Hiroki Konno^g ; Yasuhito Uezono^c ; ^h ; ⁱ ; ^{yuezono@ncc.go.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Calcium signaling ; Nociceptive pain ; Tris-hydroxymethyl aminomethane (THAM) ; TRPV cation channels ; TRPV1 receptor
• 刊名：Journal of Pharmacological Sciences
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：130
• 期：2
• 页码：72-77
• 全文大小：1113 K

文摘

Non-selective transient receptor potential vanilloid (TRPV) cation channels are activated by various insults, including exposure to heat, acidity, and the compound capsaicin, resulting in sensations of pain in the skin, visceral organs, and oral cavity. Recently, TRPV1 activation was also demonstrated in response to basic pH elicited by ammonia and intracellular alkalization. Tris-hydroxymethyl aminomethane (THAM) is widely used as an alkalizing agent; however, the effects of THAM on TRPV1 channels have not been defined. In this study, we characterized the effects of THAM-induced TRPV1 channel activation in baby hamster kidney cells expressing human TRPV1 (hTRPV1) and the Ca²⁺-sensitive fluorescent sensor GCaMP2 by real-time confocal microscopy. Notably, both capsaicin (1 μM) and pH 6.5 buffer elicited steep increases in the intracellular Ca²⁺ concentration ([Ca²⁺]_i), while treatment with THAM (pH 8.5) alone had no effect. However, treatment with THAM (pH 8.5) following capsaicin application elicited a profound, long-lasting increase in [Ca²⁺]_i that was completely inhibited by the TRPV1 antagonist capsazepine. Taken together, these results suggest that hTRPV1 pre-activation is required to provoke enhanced, THAM-induced [Ca²⁺]_i increases, which could be a mechanism underlying pain induced by basic pH.