Lesioning of TRPV1 expressing primary afferent neurons prevents PAR-2 induced motility, but not mechanical hypersensitivity in the rat colon.
Lesioning of TRPV1 expressing primary afferent neurons prevents PAR-2 induced motility, but not mechanical hypersensitivity in the rat colon.
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DOI：
10.1111/j.1365-2982.2011.01848.x
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发表时间：
2012-03
影响因子：
3.5
通讯作者：
Caudle RM
中科院分区：
文献类型：
--
作者：
Suckow SK;Anderson EM;Caudle RM
蛋白酶激活受体2（PAR-2）由结肠中的许多神经元表达，包括共表达瞬时受体电位香草素1（TRPV 1）的初级传入神经元。先前发现PAR-2受体的激活增强结肠运动，增加分泌并产生对机械刺激的超敏反应。本研究通过用高度选择性和有效的TRPV 1激动剂树脂毒素损伤TRPV 1携带神经元来检查TRPV 1/PAR-2表达神经元支配结肠的功能作用。结肠运动性在PAR-2激活的反应进行了评估，在体外使用的降结肠和在体内使用测压分离段。结肠机械伤害性阈值的测量使用结直肠扩张。用树脂毒素选择性损伤表达TRPV 1的神经元。在体外的PAR-2激动剂胰蛋白酶和SLIGRL没有改变收缩的结肠段时，单独应用，然而，代理增强乙酰胆碱刺激的收缩。在体内，PAR-2激动剂给药管腔内诱导结肠收缩，并产生对结直肠扩张的超敏反应。PAR-2激动剂增强结肠收缩时，TRPV 1表达神经元与resiniferatoxin损伤消除，但PAR-2激动剂诱导的超敏反应仍然在损伤的动物。我们的研究结果表明，TRPV 1/PAR-2表达初级传入神经元介导的外源性运动反射途径在结肠。这些数据，再加上我们以前的研究，也表明，最近描述的结肠脊髓传入神经元是伤害性的，这表明这些神经元可能是有用的目标，如肠易激综合征的疼痛的药物控制。
Proteinase activated receptor 2 (PAR-2) is expressed by many neurons in the colon, including primary afferent neurons that co-express transient receptor potential vanilloid 1 (TRPV1). Activation of PAR-2 receptors was previously found to enhance colonic motility, increase secretion and produce hypersensitivity to mechanical stimuli. This study examined the functional role of TRPV1/PAR-2 expressing neurons that innervate the colon by lesioning TRPV1 bearing neurons with the highly selective and potent TRPV1 agonist resiniferatoxin. Colonic motility in response to PAR-2 activation was evaluated in vitro using isolated segments of descending colon and in vivo using manometry. Colonic mechanical nociceptive thresholds were measured using colorectal distension. TRPV1 expressing neurons were selectively lesioned with resiniferatoxin. In vitro the PAR-2 agonists trypsin and SLIGRL did not alter contractions of colon segments when applied alone, however, the agents enhanced acetylcholine stimulated contraction. In vivo, PAR-2 agonists administered intraluminally induced contractions of the colon and produced hypersensitivity to colorectal distention. The PAR-2 agonist enhancement of colonic contraction was eliminated when TRPV1 expressing neurons were lesioned with resiniferatoxin, but the PAR-2 agonist induced hypersensitivity remained in the lesioned animals. Our findings indicate that TRPV1/PAR-2 expressing primary afferent neurons mediate an extrinsic motor reflex pathway in the colon. These data, coupled with our previous studies, also indicate that the recently described colospinal afferent neurons are nociceptive, suggesting that these neurons may be useful targets for the pharmacological control of pain in diseases such as irritable bowel syndrome.
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影响因子：
7.4
作者：
King CD;Wong F;Currie T;Mauderli AP;Fillingim RB;Riley JL 3rd
通讯作者：
Riley JL 3rd
影响因子：
3.3
作者：
Matsumoto, K.;Hosoya, T.;Horie, S.
通讯作者：
Horie, S.
影响因子：
5.5
作者：
Brierley, SM;Carter, R;Blackshaw, LA
通讯作者：
Blackshaw, LA
影响因子：
7.3
作者：
Mulè, F;Baffi, MC;Cerra, MC
通讯作者：
Cerra, MC
DOI：
10.1152/ajpgi.00137.2001
发表时间：
2002-02-01
影响因子：
4.5
作者：
Mall, M;Gonska, T;Kunzelmann, K
通讯作者：
Kunzelmann, K