Selective expression of histamine receptors H1R, H2R, and H4R, but not H3R, in the human intestinal tract
Selective expression of histamine receptors H1R, H2R, and H4R, but not H3R, in the human intestinal tract
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DOI：
10.1136/gut.2004.061762
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发表时间：
2006-04-01
期刊：
影响因子：
24.5
通讯作者：
Bischoff, SC
中科院分区：
文献类型：
--
作者：
Sander, LE;Lorentz, A;Bischoff, SC
背景和目的：组胺被认为是胃肠功能的调节剂，如胃酸产生、肠道运动和粘膜离子分泌。这些知识大部分是从动物研究中获得的。相比之下，在人类中，组胺受体（HR）在人类胃肠道中的表达和分布尚不清楚。方法：采用定量逆转录聚合酶链反应和免疫染色法分析人胃肠道组织标本中HR的表达。结果：我们发现H1R、H2R和H4R mRNA在整个胃肠道中表达，而H3R mRNA缺失。不同解剖部位（十二指肠、回肠、结肠、sigma和直肠）的HR分布无显著差异。神经元和神经纤维的免疫染色显示H3R在人肠神经系统中缺失；而在肌肠丛神经节细胞中发现了H1R和H2R。上皮细胞也表达H1R、H2R，并有一定程度的表达H4R。肠成纤维细胞只表达H1R，而人肠肌肉层的H1R和H2R均呈阳性。免疫细胞表达H1R、H2R和低水平H4R的mRNA和蛋白。对食物过敏和肠易激综合征患者的内镜活检分析显示，与对照组相比，H1R和H2R mRNA水平显著升高。结论：我们证明了H1R、H2R以及H4R在人胃肠道中有一定程度的表达，而H3R不存在，并且我们发现HR在胃肠道疾病患者中的表达发生改变。
Background and aims: Histamine is known as a regulator of gastrointestinal functions, such as gastric acid production, intestinal motility, and mucosal ion secretion. Most of this knowledge has been obtained from animal studies. In contrast, in humans, expression and distribution of histamine receptors (HR) within the human gastrointestinal tract are unclear.Methods: We analysed HR expression in human gastrointestinal tissue specimens by quantitative reverse transcription-polymerase chain reaction and immunostaining.Results: We found that H1R, H2R, and H4R mRNA were expressed throughout the gastrointestinal tract, while H3R mRNA was absent. No significant differences in the distribution of HR were found between different anatomical sites (duodenum, ileum, colon, sigma, and rectum). Immunostaining of neurones and nerve fibres revealed that H3R was absent in the human enteric nervous system; however, H1R and H2R were found on ganglion cells of the myenteric plexus. Epithelial cells also expressed H1R, H2R and, to some extent, H4R. Intestinal fibroblasts exclusively expressed H1R while the muscular layers of human intestine stained positive for both H1R and H2R. Immune cells expressed mRNA and protein for H1R, H2R, and low levels of H4R. Analysis of endoscopic biopsies from patients with food allergy and irritable bowel syndrome revealed significantly elevated H1R and H2R mRNA levels compared with controls.Conclusions: We have demonstrated that H1R, H2R and, to some extent, H4R, are expressed in the human gastrointestinal tract, while H3R is absent, and we found that HR expression was altered in patients with gastrointestinal diseases.