β-Adrenoceptors, but not dopamine receptors, mediate dopamine-induced ion transport in late distal colon of rats
β-Adrenoceptors, but not dopamine receptors, mediate dopamine-induced ion transport in late distal colon of rats
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DOI：
10.1007/s00441-008-0661-1
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发表时间：
2008-08
影响因子：
3.6
通讯作者：
Xiao-Hui Zhang;Xieping Zhang;Jiu-Qin Zhang;Yue-Min Tian;H. Xue;N. Yang;Jin-Xia Zhu
中科院分区：
文献类型：
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作者：
Xiao-Hui Zhang;Xieping Zhang;Jiu-Qin Zhang;Yue-Min Tian;H. Xue;N. Yang;Jin-Xia Zhu
多巴胺是胃肠道系统中的重要调节剂，在大鼠远端结肠中诱导浓度依赖性跨上皮离子转运，如短路电流的减少所示，并且以节段依赖性方式起作用。然而，介导多巴胺诱导的离子转运的受体是未知的。我们通过短路电流记录、实时聚合酶链反应、蛋白质印迹分析、基因转染和酶联免疫吸附试验研究了多巴胺诱导的结肠离子转运的受体机制。在大鼠远端结肠粘膜中检测到肾上腺素能受体（α、β）和多巴胺能受体（D1和D2）的mRNA转录，其中β 2表达最高。在人结肠直肠粘膜（相当于大鼠的晚期远端结肠）中发现了类似的结果。用β_1受体拮抗剂CGP-20712 A和β_2受体拮抗剂ICI 118，551预处理可分别抑制多巴胺引起的短路电流反应52.59%和92.51%。多巴胺D1受体拮抗剂SCH-23390和多巴胺D2受体拮抗剂舒必利均不能阻断多巴胺的作用。β1和β2肾上腺素能受体在大鼠远端结肠和人乙状结肠及直肠粘膜中均有蛋白表达。多巴胺能显著增加转染β1或β2肾上腺素能受体的COS-7细胞内cAMP水平。因此，β-肾上腺素受体（主要是β2-肾上腺素受体），而不是多巴胺受体，介导多巴胺诱导的大鼠远端结肠晚期离子转运。这扩展了我们对晚期远端结肠（大鼠）或结直肠（人）的认识，并提供了进一步的实验证据，可能有助于预防，诊断和临床治疗人类结直肠疾病。
Dopamine, an important modulator in the gastrointestinal system, induces concentration-dependent transepithelial ion transport in the distal colon of the rat, as shown by a decrease in the short-circuit current, and acts in a segmentally dependent manner. However, the receptor(s) that mediates dopamine-induced ion transport is unknown. We have investigated the receptor mechanisms underlying dopamine-induced colonic ion transport by means of short-circuit current recording, real-time polymerase chain reaction, and Western blotting analysis, plus gene transfection and enzyme-linked immunosorbance assay. mRNA transcripts of adrenoceptors (α, β) and dopaminergic receptors (D1and D2) were detected in the rat late distal colonic mucosa, with β2displaying the highest expression. A similar result was found in human colorectal mucosa (equivalent of late distal colon in rat). Pretreatment with a β1-adrenoceptor antagonist (CGP-20712A) and a β2-adrenoceptor antagonist (ICI 118,551) inhibited the dopamine-induced short-circuit current response by 52.59% and 92.51%, respectively. However, neither dopamine D1receptor antagonist SCH-23390 nor dopamine D2receptor antagonist sulpiride blocked the effect of dopamine. Protein expression of both β1- and β2-adrenoceptors was found in the mucosa of rat distal colon and human sigmoid colon and rectum. Dopamine significantly increased intracellular cAMP levels in COS-7 cells transfected with β1- or β2-adrenoceptors. Thus, β-adrenoceptors (mainly β2-adrenoceptors), but not dopamine receptors, mediate dopamine-induced ion transport in the late distal colon of the rat. This extends our knowledge of the late distal colon (rats) or colorectum (human) and provides further experimental evidence that might aid the prevention, diagnosis, and clinical therapy of human colorectal diseases.