Colitis affects the smooth muscle and neural response to motilin in the rabbit antrum
Colitis affects the smooth muscle and neural response to motilin in the rabbit antrum
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DOI：
10.1111/j.1476-5381.2009.00537.x
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发表时间：
2010-01-01
影响因子：
7.3
通讯作者：
Tack, Jan
中科院分区：
文献类型：
--
作者：
Depoortere, Inge;Thijs, Theo;Tack, Jan
背景和目的：肠道炎症期间或之后胃功能障碍的潜在机制知之甚少。实验方法：采用2，4，6-三硝基苯磺酸（TRB）诱导家兔结肠炎模型，5天后测定胃窦髓过氧化物酶（MPO）活性、NF-κ B（B）活性和胃动素受体密度。在离体胃窦平滑肌条中研究了平滑肌和神经对胃动素的反应。关键结果：结肠炎不影响MPO活性，但增加了胃窦NF-κ B活性。胃窦胃动素受体密度不受影响。在控制条件下，胃动素诱导缓慢发展的紧张性平滑肌收缩。炎症后5天，胃动素引起的强直性收缩减少，并在此之前出现快速的初始收缩。其他激酶被招募用于肌球蛋白轻链（MLC）（一种多功能MLC激酶）的磷酸化，以及用于抑制MLC磷酸酶（除了蛋白激酶C之外的Rho激酶）以介导炎症期间胃动素诱导的收缩。结肠炎可增强胃窦胆碱能神经的收缩。这是与胃动素的高反应性和增加肌肉反应ACh.Conclusions和影响：结肠炎改变了胃动素诱导的平滑肌收缩过程中的胃窦。这涉及磷酸化MLC的激酶的变化。胃窦胆碱能对胃动素的兴奋性增加可能在炎症相关性胃动力障碍的发病机制中起作用。英国药理学杂志（2010）159，384-393; doi：10.1111/j.1476-5381.2009.00537.x; 2009年12月4日在线发表
Background and purpose: The underlying mechanisms of gastric dysfunction during or after an episode of intestinal inflammation are poorly understood. This study investigated the effects of colitis on the contractile effects of motilin, an important endocrine regulator of gastric motility, in the antrum.Experimental approach: Myeloperoxidase (MPO) activity, NF-kappa B activity and motilin receptor density were determined in the antrum of rabbits 5 days after the induction of 2,4,6-trinitrobenzenesulphonic acid colitis. Smooth muscle and neural responses to motilin were studied in antral smooth muscle strips in vitro.Key results: Colitis did not affect MPO activity, but increased NF-kappa B activity in the antrum. Motilin receptor density in the antrum was not affected. Under control conditions, motilin induced a slowly developing tonic smooth muscle contraction. Five days post-inflammation, tonic contractions to motilin were reduced and preceded by a rapid initial contraction. Other kinases were recruited for the phosphorylation of myosin light chain (MLC) (a multi-functional MLC kinase), and for the inhibition of MLC phosphatase (Rho kinase in addition to protein kinase C) to mediate the motilin-induced contractions during inflammation. Colitis potentiated the cholinergic neural on-contractions in the antrum. This was associated with a hyper-reactivity to motilin and an increased muscle response to ACh.Conclusions and implications: Colitis altered the course of the motilin-induced smooth muscle contraction in the antrum. This involved changes in the kinases phosphorylating MLC. Increased cholinergic excitability to motilin in the antrum may play a role in the pathogenesis of inflammation-associated gastric motility disorders. British Journal of Pharmacology (2010) 159, 384-393; doi: 10.1111/j.1476-5381.2009.00537.x; published online 4 December 2009