Schicho Rudolf, Florian Waltraud, Liebmann Ingrid, Holzer Peter, Lippe Irmgard Th
Department of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
Eur J Neurosci. 2004 Apr;19(7):1811-8. doi: 10.1111/j.1460-9568.2004.03290.x.
It is still unknown which receptors of peripheral sensory pathways encode and integrate an acid-induced nociceptive event in the gastric mucosa. The transient receptor potential vanilloid receptor 1 (TRPV1) and the acid-sensing ion channel 3 (ASIC3) are two nociception-related receptors. Here we investigated (i) to what extent these receptors are distributed in stomach-innervating neurons of dorsal root and nodose ganglia, using immunohistochemistry and retrograde tracing, and (ii) whether their expression is altered in response to a noxious acid challenge of the stomach. We also explored the presence of TRPV1 in the gastric enteric nervous system because of its possible expression by intrinsic sensory neurons. Most stomach-innervating neurons in nodose ganglia were immunoreactive for TRPV1 (80%) and ASIC3 (75%), these results being similar in the dorsal root ganglia (71 and 82%). RT-PCR and Western blotting were performed up to 6 h after oral application of 0.5 m HCl to conscious rats. TRPV1 protein was increased in dorsal root but not in nodose ganglia whereas TRPV1 and ASIC3 mRNAs remained unchanged. TRPV1 mRNA was detected in longitudinal muscle-myenteric plexus preparations of control stomachs and was not altered by the acid challenge. Combined vagotomy and ganglionectomy abolished expression of TRPV1, indicating that it may derive from an extrinsic source. In summary, noxious acid challenge of the stomach increased TRPV1 protein in spinal but not vagal or intrinsic sensory afferents. The TRPV1 receptor may be a key molecule in the transduction of acid-induced nociception of the gastric mucosa and a mediator of visceral hypersensitivity.
目前尚不清楚外周感觉通路的哪些受体编码并整合胃黏膜中酸诱导的伤害性事件。瞬时受体电位香草酸受体1（TRPV1）和酸敏感离子通道3（ASIC3）是两种与伤害感受相关的受体。在这里，我们进行了以下研究：（i）使用免疫组织化学和逆行追踪技术，探究这些受体在背根神经节和结状神经节支配胃的神经元中的分布程度；（ii）它们的表达是否会因胃受到有害酸刺激而发生改变。由于TRPV1可能由内在感觉神经元表达，我们还探索了其在胃肠神经系统中的存在情况。结状神经节中大多数支配胃的神经元对TRPV1（80%）和ASIC3（75%）呈免疫反应性，背根神经节中的结果与之相似（分别为71%和82%）。给清醒大鼠口服0.5 m HCl后6小时内进行逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测。背根神经节中TRPV1蛋白增加，但结状神经节中未增加，而TRPV1和ASIC3的信使核糖核酸（mRNA）保持不变。在对照胃的纵行肌-肌间神经丛制剂中检测到TRPV1 mRNA，但酸刺激未使其改变。联合迷走神经切断术和神经节切除术消除了TRPV1的表达，表明它可能来源于外在来源。总之，胃受到有害酸刺激会增加脊髓而非迷走神经或内在感觉传入纤维中TRPV1蛋白的表达。TRPV1受体可能是胃黏膜酸诱导伤害感受转导中的关键分子，也是内脏超敏反应的介质。
