Penuelas Angelica, Tashima Kimihito, Tsuchiya Shizuko, Matsumoto Kenjiro, Nakamura Tomonori, Horie Syunji, Yano Shingo
Department of Molecular Pharmacology and Pharmacotherapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan.
Eur J Pharmacol. 2007 Dec 8;576(1-3):143-50. doi: 10.1016/j.ejphar.2007.08.015. Epub 2007 Aug 17.
TRPA1 is a member of the transient receptor potential (TRP) channel family expressed in sensory neurons. The present study focused on the effects of TRPA1 activation on contractile responses in isolated mouse intestine preparations. The jejunum, ileum, and proximal and distal colon were surgically isolated from male ddY mice. Intestinal motility was recorded as changes in isotonic tension. TRPA1, TRPM8, and TRPV1 expressions were examined by reverse transcription-polymerase chain reaction (RT-PCR). A TRPA1 agonist allyl isothiocyanate (AITC) dose-dependently induced contractions in the proximal and distal colon, whereas in the jejunum and ileum, even 100 muM AITC caused very little contraction. Likewise, a TRPA1 and TRPM8 agonist icilin, a TRPA1 agonist allicin, and a TRPV1 agonist capsaicin induced contractions in the colon. However, a TRPM8 agonist menthol induced long-lasting relaxation in the colon. Repeated exposure to AITC produced desensitization of its own contraction in the colon. Moreover, contractions induced by AITC generate cross-desensitization with icilin and capsaicin. Tetrodotoxin completely abolished AITC-induced contractions in the colon, whereas atropine significantly attenuated AITC-induced contractions in the distal colon, but not in the proximal colon. Menthol-induced relaxation in the colon was not inhibited by tetrodotoxin and atropine. RT-PCR analysis revealed the expression of TRPA1 and TRPV1, but not TRPM8, throughout the mouse intestine. These results suggest that TRPA1, but not TRPM8, are functionally expressed in the enteric nervous system throughout the mouse intestine on neurons that may also co-express TRPV1, yet the contractile responses to TRPA1 activation differ depending on their location along the intestine.
TRPA1是瞬时受体电位（TRP）通道家族的成员，在感觉神经元中表达。本研究聚焦于TRPA1激活对分离的小鼠肠道标本收缩反应的影响。从雄性ddY小鼠身上手术分离出空肠、回肠以及近端和远端结肠。肠道运动以等张张力的变化来记录。通过逆转录聚合酶链反应（RT-PCR）检测TRPA1、TRPM8和TRPV1的表达。TRPA1激动剂异硫氰酸烯丙酯（AITC）剂量依赖性地诱导近端和远端结肠收缩，而在空肠和回肠中，即使100μM的AITC也只能引起极少的收缩。同样，TRPA1和TRPM8激动剂冰片、TRPA1激动剂大蒜素以及TRPV1激动剂辣椒素均可诱导结肠收缩。然而，TRPM8激动剂薄荷醇可诱导结肠产生持久的舒张。反复暴露于AITC会使其自身在结肠中的收缩产生脱敏现象。此外，AITC诱导的收缩会与冰片和辣椒素产生交叉脱敏。河豚毒素完全消除了AITC在结肠中诱导的收缩，而阿托品显著减弱了AITC在远端结肠中的收缩，但对近端结肠无效。薄荷醇诱导的结肠舒张不受河豚毒素和阿托品的抑制。RT-PCR分析显示，在整个小鼠肠道中均有TRPA1和TRPV1的表达，但未检测到TRPM8的表达。这些结果表明，TRPA1而非TRPM8在整个小鼠肠道的肠神经系统中功能性表达，这些神经元可能也共表达TRPV1，然而对TRPA1激活的收缩反应因其在肠道中的位置不同而有所差异。
