Taniguchi M, Mashita Y, Matsuzaka Y, Kato S, Takeuchi K
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, 607-8414, Japan.
Inflammopharmacology. 2007 Dec;15(6):273-7. doi: 10.1007/s10787-007-1586-0.
We investigated the role of capsaicin-sensitive afferent neurons in receptive relaxation of the rat stomach in response to distension. Under urethane anesthesia, a balloon with barostat was inserted through the pylorus and placed in the forestomach. Isobaric distension was performed in a stepwise increment of 2 mmHg, each lasting for 2 min, while the corresponding intragastric volume was recorded. Gastric distension produced the intraballoon volume in a progressive manner with saturation, suggesting the occurrence of receptive relaxation of the stomach during distension. Intragastric application of capsaicin significantly enhanced the degree of receptive relaxation. The capsaicin-induced enhancement of receptive relaxation was totally abolished by bilateral vagotomy as well as chemical ablation of capsaicin-sensitive afferent neurons. Likewise, the enhanced receptive relaxation in response to stomach distension was also significantly attenuated by pretreatment of the animals with NG-nitro-L-arginine methyl ester (L-NAME, an inhibitor of nitric oxide (NO) synthase), calcitonin gene related peptide (CGRP)8-37 (CGRP antagonist), indomethacin and ONO-8711 (EP1 receptor antagonist). These results suggest that capsaicin significantly enhanced the receptive relaxation induced by gastric distention through both vagal nerves and capsaicin-sensitive afferent neurons. This process is intervened by endogenous NO and CGRP in addition to prostaglandins (PGs), and the effect of PGs may be mediated by EP1 receptors.
我们研究了辣椒素敏感传入神经元在大鼠胃对扩张的适应性舒张反应中的作用。在乌拉坦麻醉下,将带有压力调节器的气囊经幽门插入并置于前胃。以2 mmHg的增量逐步进行等压扩张,每次持续2分钟,同时记录相应的胃内体积。胃扩张使气囊内体积呈渐进性饱和增加,提示胃在扩张过程中发生了适应性舒张。胃内应用辣椒素显著增强了适应性舒张程度。辣椒素诱导的适应性舒张增强被双侧迷走神经切断术以及辣椒素敏感传入神经元的化学消融完全消除。同样,用NG-硝基-L-精氨酸甲酯(L-NAME,一种一氧化氮(NO)合酶抑制剂)、降钙素基因相关肽(CGRP)8-37(CGRP拮抗剂)、吲哚美辛和ONO-8711(EP1受体拮抗剂)预处理动物后,对胃扩张的增强适应性舒张也显著减弱。这些结果表明,辣椒素通过迷走神经和辣椒素敏感传入神经元显著增强了胃扩张诱导的适应性舒张。这一过程除了前列腺素(PGs)外,还受到内源性NO和CGRP的干预,PGs的作用可能由EP1受体介导。