Centre for Gastroenterological Research, Catholic University of Leuven, Leuven, Belgium.
Br J Pharmacol. 2010 Jan 1;159(2):384-93. doi: 10.1111/j.1476-5381.2009.00537.x. Epub 2009 Dec 4.
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.
Myeloperoxidase (MPO) activity, NF-kappaB 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.
Colitis did not affect MPO activity, but increased NF-kappaB 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.
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.
肠道炎症期间或之后胃功能障碍的潜在机制尚未完全阐明。本研究旨在研究结肠炎对胃动素收缩效应的影响，胃动素是胃运动的重要内分泌调节剂。
在 2,4,6-三硝基苯磺酸结肠炎诱导后 5 天，测定兔胃窦中髓过氧化物酶（MPO）活性、NF-κB 活性和胃动素受体密度。在体外胃窦平滑肌条上研究平滑肌和神经对胃动素的反应。
结肠炎不影响 MPO 活性，但增加胃窦 NF-κB 活性。胃窦内胃动素受体密度不受影响。在对照条件下，胃动素诱导缓慢发展的紧张性平滑肌收缩。炎症后 5 天，胃动素引起的紧张性收缩减少，并伴有快速初始收缩。其他激酶被招募用于肌球蛋白轻链（MLC）的磷酸化（多功能 MLC 激酶），并用于抑制 MLC 磷酸酶（除蛋白激酶 C 外，还为 Rho 激酶），以介导炎症期间胃动素诱导的收缩。结肠炎增强了胃窦中的胆碱能神经非收缩。这与对胃动素的超反应性和对 ACh 的肌肉反应增加有关。
结肠炎改变了胃窦中胃动素诱导的平滑肌收缩过程。这涉及到磷酸化 MLC 的激酶发生变化。胃窦中对胃动素的胆碱能兴奋性增加可能在炎症相关胃动力障碍的发病机制中起作用。
