Role of Histaminergic Neurons in Brain-GUT Interactions

这项研究的目的是验证内脏刺激诱导神经递质释放的假设，尤其是大脑中的组胺。第二种假设是释放的组胺在调节大脑功能中起作用。我们期望这样的分析将导致识别脑-肠相互作用中的物质。用雄性Wistar大鼠进行微透析实验。大鼠结肠膨胀诱导海马组胺从1.34±0.47pmol/l显著升高至4.68±0.58pmol/l （p<0.05）。大鼠在结直肠膨胀后暴露于升高的迷宫中，可诱发焦虑相关行为。大鼠结肠膨胀也诱导海马释放去甲肾上腺素。非特异性促肾上腺皮质激素释放激素（CRH）受体拮抗剂α-螺旋CRH或特异性CRH受体-1 （CRH- r1）拮抗剂JTC017均可阻断这些变化。用回旋加速器合成的H_2^<15>O，用正电子发射断层扫描（PET）检测脑血流（rCBF）。分析结肠扩张下的PET图像。此外，静脉注射选择性组胺H1受体拮抗剂d-氯苯那敏，并分析PET图像。结肠扩张诱导丘脑、前扣带皮层和前额叶皮层rCBF增加。同时，结肠扩张诱导内脏感知和情绪。这些变化明显减弱给药和d-氯苯那敏。在肠易激综合征（IBS）患者中，左前额叶皮层被激活。这些结果表明，组胺、去甲肾上腺素和CRH是通过结肠扩张在大脑边缘系统释放的，而组胺H1受体和CRH- r1至少部分参与了这些现象。这些结果可能为使用组胺H1受体拮抗剂或CRH-R1拮抗剂治疗脑肠相互作用的病理生理状况打开了大门。少

The aim of this study was to test the hypothesis that visceral stimulation induces neurotransmitter release, especially histamine, in the brain. The second hypothesis is that released histamine plays a role in modulating brain function. We expected that such analysis would result in identifying substance in brain-gut interactions. Microdilalysis experiment was performed using male Wistar rats. Colorectal distension of rats induced significant increase in histamine in the hippocampus from 1.34±0.47pmol/l to 4.68±0.58pmol/l (p<0.05). Anxiety-related behaviors were evoked when the rats were exposed to elevated plus maze after colorectal distention. Colorectal distention of rats also induced noradrenaline release in the hippocampus. These changes were blocked by administration of either non-specific corticotropin-releasing hormone (CRH) receptor antagonist α-helical CRH or specific CRH receptor-1 (CRH-R1) antagonist JTC017. In humans, positron emission tomography (PET) was performed for de … More tecting regional cerebral blood flow (rCBF) using H_2^<15>O which was synthesized with cyclotron. PET image under colonic distention was analyzed. Moreover, selective histamine H1 receptor antagonist d-chlorpheniramine was administered intravenously and PET image was analyzed. Colonic distention induced increase in rCBF in the thalamus, the anterior cingulate cortex, and the prefrontal cortex. Simultaneously, colonic distention inducedvisceral perception and emotion. These changes were significantly attenuated by administration and of d-chlorpheniramine. In patients with irritable bowel syndrome (IBS), left prefrontal cortex was activated. These results suggest that histamine noradrenaline, and CRH are released in the limbic system of the brain by colonic distention and that at least in part histamine H1 receptor and CRH-R1 are involved these phenomena. These results may open the door of possible therapeutic use of histamine H1 receptor antagonist or CRH-R1 antagonist for pathophysiological condition of brain-gut interactions. Less