Dopamine receptor D1 mediates the inhibition of dopamine on the distal colonic motility.
Dopamine receptor D1 mediates the inhibition of dopamine on the distal colonic motility.
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DOI：
10.1016/j.trsl.2012.01.002
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发表时间：
2012-05
期刊：
影响因子：
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通讯作者：
Xiaohui Zhang;Hua Guo;Jindong Xu;Yun Li;Lisheng Li;Xiaoli Zhang;Xiaofeng Li;Ruifang Fan;Yue Zhang;Zhongping Duan;Jinxia Zhu
中科院分区：
文献类型：
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作者：
Xiaohui Zhang;Hua Guo;Jindong Xu;Yun Li;Lisheng Li;Xiaoli Zhang;Xiaofeng Li;Ruifang Fan;Yue Zhang;Zhongping Duan;Jinxia Zhu
多巴胺（DA）可抑制远端结肠的运动，但有关多巴胺受体的研究还存在争议。本研究旨在探讨DA受体介导的DA对大鼠结肠运动的抑制作用。用等长测力传感器测定离体结肠条的收缩力。免疫荧光法和Western blot法检测远端结肠DA受体的表达。用液相色谱/质谱法测定结肠平滑肌中DA的浓度。结果表明，DA对结肠自发运动有明显的抑制作用，其EC值为8.3 μM，并呈剂量依赖性。河豚毒素增加结肠收缩频率，但不影响DA对结肠运动的抑制作用。多巴胺D1受体拮抗剂SCH-23390预处理使量效曲线右移，DA的EC 50为37 μM。而舒必利阻断多巴胺D2受体则无此作用。D1和D2在远端结肠肌间神经丛和平滑肌中呈阳性反应。急性冷束缚应激（CRS）可增强大鼠远端结肠的自发性收缩，且对DA更为敏感。CRS条件下，平滑肌层DA含量和D1表达增加。结论：平滑肌中的D1介导了DA对大鼠远端结肠自发收缩的抑制作用。结肠平滑肌层DA含量和D1受体表达的增加可能是CRS条件下结肠运动增强的一种代偿效应。
The motility of distal colon could be inhibited by dopamine (DA), yet, the involved receptor is controversial according to the published reports. The goal of present study was to investigate DA receptor(s) mediated inhibition of DA on the colonic motility in rat. The contraction of isolated colon strips was assessed through isometric force transducer. The expressions of DA receptors in distal colon were detected through immunofluorescence and Western blot. DA concentration in colonic smooth muscle was measured by liquid chromatography/mass spectrometry. The results showed that DA inhibited the spontaneous motility of distal colon in a dose-dependent manner with EC508.3 μM. Tetrodotoxin increased colonic contractive frequency, but failed to affect the inhibition of DA on the colonic motility. Pretreatment with SCH-23390, an antagonist of dopaminergic receptor D1, shifted the dose-response curve to the right with EC50of DA 37 μM. However, blocking dopaminergic receptor D2with sulpiride, had no effect. The immunoreactivity of D1and D2were detected in the distal colon including myenteric plexus and smooth muscle. Acute cold-restraint stress (CRS) enhanced spontaneous contraction of rat distal colon, which was more sensitive to DA compared with control. Moreover, DA content and D1expression in smooth muscle layer were increased under CRS condition. In conclusion, D1in the smooth muscle is mediated DA inhibition on the spontaneous contraction of rat distal colon. The increased DA content and D1receptor expression in the smooth muscle layer could be a compensatory effect under CRS condition to balance the enhanced colonic motility.