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鉴定组氨酸受体以及组氨酸对鼠类和灵长类结肠兴奋性的影响。

Identification of histamine receptors and effects of histamine on murine and simian colonic excitability.

机构信息

Department of Internal Medicine, School of Medicine, Gyeongsang National University, Jinju, Korea.

出版信息

Neurogastroenterol Motil. 2011 Oct;23(10):949-e409. doi: 10.1111/j.1365-2982.2011.01760.x. Epub 2011 Aug 1.

DOI:10.1111/j.1365-2982.2011.01760.x
PMID:21806740
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3173574/
Abstract

BACKGROUND

Inflammatory responses can include recruitment of cells of hematopoietic origin to the tunica muscularis. These cells can secrete a variety of factors which can reset the gain of smooth muscle cells (SMC) and influence motor patterns. Histamine (H), a major mediator in inflammation, is released by mast cells and exerts diverse effects in SMC by binding to H receptors. The profiles of H receptor expression in animal models used to study inflammatory diseases are unknown.

METHODS

Histamine receptor expression and electro-mechanical responses to H were tested in simian and murine colonic smooth muscle using qualitative and quantitative PCR, isometric force measurements, microelectrode recordings and patch clamp techniques.

KEY RESULTS

H1, H2, and H4 receptor transcripts were expressed at similar levels in simian colonic tissue whereas only the H2 receptor transcript was detected in murine colonic tissue. Stimulation of simian colonic muscles with H caused depolarization and contraction in the presence of tetrodotoxin. Histamine activated non-selective cation channels in simian SMC. In contrast, H caused hyperpolarization and inhibited contractions of murine colon. The hyperpolarization was inhibited by the K(ATP) channel blocker, glibenclamide. Histamine-activated K(+) currents were inhibited by glibenclamide in murine colonic SMC.

CONCLUSIONS & INFERENCES: Histamine receptor expression in simian SMC was similar to that reported in humans. However, H receptor profile and responses to H were considerably different in mice. Thus, monkey colon may be a more suitable model to study how inflammatory mediators affect the gain of smooth muscle excitability.

摘要

背景

炎症反应可包括造血细胞向肌层的募集。这些细胞可以分泌多种因子,重新设定平滑肌细胞(SMC)的增益,并影响运动模式。组胺(H)是炎症中的主要介质,由肥大细胞释放,并通过与 H 受体结合在 SMC 中发挥多种作用。用于研究炎症性疾病的动物模型中 H 受体表达的特征尚不清楚。

方法

使用定性和定量 PCR、等长力测量、微电极记录和膜片钳技术,测试灵长类和鼠结肠平滑肌中 H 受体表达和对 H 的机电反应。

主要结果

H1、H2 和 H4 受体转录本在灵长类结肠组织中的表达水平相似,而在鼠结肠组织中仅检测到 H2 受体转录本。H 刺激灵长类结肠肌肉在四氮唑存在下引起去极化和收缩。组胺激活灵长类 SMC 中的非选择性阳离子通道。相比之下,H 引起鼠结肠的超极化和抑制收缩。超极化被 K(ATP)通道阻滞剂格列本脲抑制。格列本脲抑制鼠结肠 SMC 中的 H 激活的 K(+)电流。

结论和推论

灵长类 SMC 中的 H 受体表达与人类报道的相似。然而,H 受体谱和对 H 的反应在小鼠中差异很大。因此,猴子结肠可能是研究炎症介质如何影响平滑肌兴奋性增益的更合适模型。

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