Role of enteric dopaminergic neurons in regulating peristalsis of rat proximal colon
Role of enteric dopaminergic neurons in regulating peristalsis of rat proximal colon
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DOI：
10.1111/nmo.14127
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发表时间：
2021-05-03
影响因子：
3.5
通讯作者：
Hashitani, Hikaru
中科院分区：
文献类型：
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作者：
Nakamori, Hiroyuki;Noda, Kenta;Hashitani, Hikaru
研究背景便秘常见于帕金森氏病患者，与中枢和肠道神经系统多巴胺能神经元丢失有关。然而，肠多巴胺能神经元在便秘发生中的作用仍有待阐明。方法将大鼠近端结肠的空肠段置于脏器浴中，以生理盐液进行灌流，以0.9%生理盐水照亮灌流。在洗涤液中涂抹药物。一台摄像机捕捉到结肠段直径沿长度的变化，并将其转换为时空地图。关键结果阻断氮能神经传递可阻止蠕动波的口-口传播，并引起结肠收缩，而不影响波纹和非传播性肌源性收缩。阻断胆碱能神经传递也能阻止蠕动波，但通过结肠扩张抑制涟漪。河豚毒素(0.6 mM)使蠕动波消失，收缩时波纹增多。D-1样多巴胺受体拮抗剂SCH 23390(20 MU M)使蠕动波减慢并引起收缩，而多巴胺再摄取抑制剂GBR 12909(1 MU M)则通过扩张使蠕动波减弱。沐浴应用多巴胺(3微米)以SCH 23390(5微米)敏感的方式消除与结肠扩张相关的蠕动波。结论多巴胺能神经元可能通过D-1受体促进硝能神经元稳定非同步收缩活动，从而导致结肠蠕动的产生。
Background Constipation is commonly seen in patients with Parkinson's disease associated with a loss of dopaminergic neurons in both central and enteric nervous systems. However, the roles of enteric dopaminergic neurons in developing constipation remain to be elucidated. Here, we investigated the roles of enteric dopaminergic neurons in the generation of colonic peristalsis.Methods Cannulated segments of rat proximal colon were situated in the organ bath, abluminally perfused with physiological salt solution and luminally perfused with 0.9% saline. Drugs were applied in the abluminal solution. Changes in diameter along the length of the colonic segment were captured by a video camera and transformed into spatio-temporal maps. Fluorescence immunohistochemistry was also carried out.Key Results Blockade of nitrergic neurotransmission prevented oro-aboral propagation of peristaltic waves and caused a colonic constriction without affecting ripples, non-propagating myogenic contractions. Blockade of cholinergic neurotransmission also prevented peristaltic waves but suppressed ripples with a colonic dilatation. Tetrodotoxin (0.6 mu M) abolished peristaltic waves and increased ripples with a constriction. SCH 23390 (20 mu M), a D-1-like dopamine receptor antagonist, slowed the peristaltic waves and caused a constriction, while GBR 12909 (1 mu M), a dopamine reuptake inhibitor, diminished the peristaltic waves with a dilatation. Bath-applied dopamine (3 mu M) abolished the peristaltic waves associated with a colonic dilation in an SCH 23390 (5 mu M)-sensitive manner. D-1 receptor immunoreactivity was co-localized to nitrergic and cholinergic neurons.Conclusions and Inferences Dopaminergic neurons appear to facilitate nitrergic neurons via D-1-like receptors to stabilize asynchronous contractile activity resulting in the generation of colonic peristalsis.