Stomach-brain communication by vagal afferents in response to luminal acid backdiffusion, gastrin, and gastric acid secretion
Stomach-brain communication by vagal afferents in response to luminal acid backdiffusion, gastrin, and gastric acid secretion
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DOI：
10.1152/ajpgi.00308.2003
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发表时间：
2004-03-01
影响因子：
4.5
通讯作者：
Holzer, P
中科院分区：
文献类型：
--
作者：
Danzer, M;Jocic, M;Holzer, P
迷走神经传入在生理和病理刺激的肠脑信号传导中发挥作用。在这里，我们研究了腔内 HCl 或 NH4OH 的反向扩散与五肽胃泌素刺激的酸分泌在大鼠胃和脑干之间的通讯中如何相互作用。在胃内给予盐水或反向扩散浓度的HCl或NH4OH之前，用媒介物或适当剂量的西咪替丁、奥美拉唑、五肽胃泌素、右旋酰脲（CCK1受体拮抗剂）和伊曲脲（CCK2受体拮抗剂）对大鼠进行腹腔内预处理。两小时后，通过 c-Fos 免疫组织化学观察孤束核 (NTS) 和后区的神经元激活。将大鼠胃粘膜暴露于 HCl (0.15-0.5 M) 或 NH4OH (0.1-0.3 M) 导致 NTS 中 c-Fos 的浓度依赖性表达，这与性别、胃粘膜损伤或胃幽门运动改变无关。 c-Fos 对 HCl 的反应被西咪替丁和奥美拉唑减弱，被五肽胃泌素增强，而右旋酰脲和伊曲鲁胺则保持不变。单独的五肽胃泌素引起c-fos的奥美拉唑抗性表达，在NTS中，这种表达被伊曲鲁米特减弱，并被右旋米特阻止，但在后部区域，这种表达被右旋米特减少，并被伊曲鲁米特消除。我们得出结论，迷走神经传入将生理刺激（胃泌素）和病理事件（腔内 HCl 或 NH4OH 的反向扩散）从胃传递到脑干。这些通讯方式相互作用，因为首先，酸分泌增强了胃酸反向扩散的传入信号传导，其次，胃泌素通过刺激迷走神经传入上的 CCK1 受体和投射到 NTS 的后区神经元上的 CCK2 受体来激活 NTS 神经元。
Vagal afferents play a role in gut-brain signaling of physiological and pathological stimuli. Here, we investigated how backdiffusion of luminal HCl or NH4OH and pentagastrin-stimulated acid secretion interact in the communication between rat stomach and brain stem. Rats were pretreated intraperitoneally with vehicle or appropriate doses of cimetidine, omeprazole, pentagastrin, dexloxiglumide (CCK1 receptor antagonist), and itriglumide (CCK2 receptor antagonist) before intragastric administration of saline or backdiffusing concentrations of HCl or NH4OH. Two hours later, neuronal activation in the nucleus of the solitary tract (NTS) and area postrema was visualized by c-Fos immunohistochemistry. Exposure of the rat gastric mucosa to HCl (0.15-0.5 M) or NH4OH (0.1-0.3 M) led to a concentration-dependent expression of c-Fos in the NTS, which was not related to gender, gastric mucosal injury, or gastropyloric motor alterations. The c-Fos response to HCl was diminished by cimetidine and omeprazole, enhanced by pentagastrin, and left unchanged by dexloxiglumide and itriglumide. Pentagastrin alone caused an omeprazole-resistant expression of c-fos, which in the NTS was attenuated by itriglumide and prevented by dexloxiglumide but in the area postrema was reduced by dexloxiglumide and abolished by itriglumide. We conclude that vagal afferents transmit physiological stimuli (gastrin) and pathological events (backdiffusion of luminal HCl or NH4OH) from the stomach to the brain stem. These communication modalities interact because, firstly, acid secretion enhances afferent signaling of gastric acid backdiffusion and, secondly, gastrin activates NTS neurons through stimulation of CCK1 receptors on vagal afferents and of CCK2 receptors on area postrema neurons projecting to the NTS.