Nitrergic signaling via interstitial cells of Cajal and smooth muscle cells influences circular smooth muscle contractility in murine colon
Nitrergic signaling via interstitial cells of Cajal and smooth muscle cells influences circular smooth muscle contractility in murine colon
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DOI：
10.1111/nmo.13300
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发表时间：
2018-06-01
影响因子：
3.5
通讯作者：
Voussen, B.
中科院分区：
文献类型：
--
作者：
Beck, K.;Friebe, A.;Voussen, B.
背景胃肠运动的调节涉及兴奋性和抑制性神经传递。一氧化氮（NO）是主要的抑制性神经递质，通过其受体NO敏感的鸟苷酸环化酶（NO-GC）发挥作用。在胃肠道中，NO-GC在几种细胞类型中表达，例如平滑肌细胞（SMC）和Cajal间质细胞（ICC）。使用细胞特异性基因敲除小鼠，我们先前已经表明，NO-GC调节结肠纵向平滑肌的自发收缩。然而，其详细的作用，在结肠环形平滑肌仍不清楚。MethodsMyography进行评估自发收缩环近端结肠（2.5毫米）从全球（GCKO）和细胞特异性敲除小鼠NO-GC。免疫组织化学和原位杂交技术用于确定NO-GC的表达。Key resultsColonic circular smooth muscle显示了三种不同的收缩模式：高频波纹，慢相收缩和大收缩。波纹形成独立于NO-GC。慢相收缩在WT、SMC-GCKO和ICC-GCKO组织中间歇性发生，而在GCKO和SMC/ICC-GCKO组织中更显著和延长。河豚毒素和NO-GC抑制剂ODQ将WT和单细胞特异性敲除的慢相收缩转化为GCKO样收缩。ODQ增加WT和ICC-GCKO结肠的大收缩频率，但在GCKO、SMC-GCKO和SMC/ICC-GCKO制剂中不增加。河豚毒素和六烃季铵废除大contractions.Conclusions和InferencesWe得出结论，小鼠结肠短环可以有效地用于记录自发性收缩。虽然SMC中的NO-GC决定平滑肌张力，但SMC和ICC中的NO-GC的协同作用调节慢相收缩和大收缩。
BackgroundRegulation of gastrointestinal motility involves excitatory and inhibitory neurotransmission. Nitric oxide (NO), the major inhibitory neurotransmitter, acts via its receptor NO-sensitive guanylyl cyclase (NO-GC). In the GI tract, NO-GC is expressed in several cell types such as smooth muscle cells (SMC) and interstitial cells of Cajal (ICC). Using cell-specific knockout mice, we have previously shown that NO-GC modulates spontaneous contractions in colonic longitudinal smooth muscle. However, its detailed role in the colonic circular smooth muscle is still unclear.MethodsMyography was performed to evaluate spontaneous contractions in rings of proximal colon (2.5mm) from global (GCKO) and cell-specific knockout mice for NO-GC. Immunohistochemistry and in situ hybridization were used to specify NO-GC expression.Key resultsColonic circular smooth muscle showed three different contraction patterns: high-frequency ripples, slow phasic contractions, and large contractions. Ripples formed independently of NO-GC. Slow phasic contractions occurred intermittently in WT, SMC-GCKO, and ICC-GCKO tissue, whereas they were more prominent and prolonged in GCKO and SMC/ICC-GCKO tissue. Tetrodotoxin and the NO-GC inhibitor ODQ transformed slow phasic contractions of WT and single cell-specific knockout into GCKO-like contractions. ODQ increased the frequency of large contractions in WT and ICC-GCKO colon but not in GCKO, SMC-GCKO, and SMC/ICC-GCKO preparations. Tetrodotoxin and hexamethonium abolished large contractions.Conclusions and InferencesWe conclude that short rings of murine colon can be effectively used to record spontaneous contractions. Although NO-GC in SMC determines smooth muscle tone, concerted action of NO-GC in both SMC and ICC modulates slow phasic contractions and large contractions.