Involvement of the P2X7 purinergic receptor in colonic motor dysfunction associated with bowel inflammation in rats.
Involvement of the P2X7 purinergic receptor in colonic motor dysfunction associated with bowel inflammation in rats.
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DOI：
10.1371/journal.pone.0116253
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Fornai M
中科院分区：
文献类型：
--
作者：
Antonioli L;Giron MC;Colucci R;Pellegrini C;Sacco D;Caputi V;Orso G;Tuccori M;Scarpignato C;Blandizzi C;Fornai M
最近的证据表明，P2X7嘌呤能受体(P2X7R)参与了免疫功能的微调，也参与了肠道炎症状态下肠神经细胞的凋亡。然而，该受体在肠道神经肌肉功能调节中的作用仍不确定。本研究旨在探讨P2X7Rs在实验性结肠炎结肠运动控制中的作用。用2，4-二硝基苯磺酸诱导大鼠结肠炎。免疫荧光分析法检测P2X7R的分布。本实验观察了选择性P2X7R拮抗剂A804598和P2X7R激动剂BzATP对电刺激和河豚毒素引起的卡巴胆碱引起的纵行肌条收缩的影响。P2X7Rs主要定位于肌间神经元，但在结肠炎时，其在神经肌肉层的表达增加。在正常的制剂中，A804598引起的电诱导收缩的增加可以忽略不计，而在炎症组织中记录到显著的增强。在神经元型一氧化氮合酶抑制剂N-丙基-L-精氨酸存在下，A804598的作用消失。在正常结肠中，用BzATP刺激P2X7R对电诱导的收缩没有显著影响，而在炎症条件下记录到明显的减少。BzATP的抑制作用可被A804598拮抗，也可被NPA明显钝化。两种P2X7R配体均不影响氨基甲胆碱引起的收缩。嘌呤能系统通过P2X7Rs参与肠道炎症相关的功能性神经肌肉改变，该受体通过对抑制性氮能通路的易化控制来调节兴奋性胆碱能神经的活动。
Recent evidence indicates an involvement of P2X7 purinergic receptor (P2X7R) in the fine tuning of immune functions, as well as in driving enteric neuron apoptosis under intestinal inflammation. However, the participation of this receptor in the regulation of enteric neuromuscular functions remains undetermined. This study was aimed at investigating the role of P2X7Rs in the control of colonic motility in experimental colitis. Colitis was induced in rats by 2,4-dinitrobenzenesulfonic acid. P2X7R distribution was examined by immunofluorescence analysis. The effects of A804598 (selective P2X7R antagonist) and BzATP (P2X7R agonist) were tested on contractions of longitudinal smooth muscle evoked by electrical stimulation or by carbachol in the presence of tetrodotoxin. P2X7Rs were predominantly located in myenteric neurons, but, in the presence of colitis, their expression increased in the neuromuscular layer. In normal preparations, A804598 elicited a negligible increase in electrically induced contractions, while a significant enhancement was recorded in inflamed tissues. In the presence of Nω-propyl-L-arginine (NPA, neuronal nitric oxide synthase inhibitor) the A804598 effects were lost. P2X7R stimulation with BzATP did not significantly affect electrical-induced contractions in normal colon, while a marked reduction was recorded under inflammation. The inhibitory effect of BzATP was antagonized by A804598, and it was also markedly blunted by NPA. Both P2X7R ligands did not affect carbachol-induced contractions. The purinergic system contributes to functional neuromuscular changes associated with bowel inflammation via P2X7Rs, which modulate the activity of excitatory cholinergic nerves through a facilitatory control on inhibitory nitrergic pathways.
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影响因子：
13.6
作者：
Antonioli L;Pacher P;Vizi ES;Haskó G
通讯作者：
Haskó G
DOI：
10.1038/nri2938
发表时间：
2011-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
9.3
作者：
Lakhan SE;Kirchgessner A
通讯作者：
Kirchgessner A
DOI：
10.1152/ajpgi.00358.2010
发表时间：
2011-01-01
影响因子：
4.5
作者：
Shi, Xuan-Zheng;Winston, John H.;Sarna, Sushil K.
通讯作者：
Sarna, Sushil K.
DOI：
10.1016/j.bbadis.2013.10.012
发表时间：
2014-01-01
影响因子：
6.2
作者：
Marques, Carla Caldas;Castelo-Branco, Morgana T.;de Souza, Heitor S. P.
通讯作者：
de Souza, Heitor S. P.