Takeuchi K, Matsumoto J, Ueshima K, Okabe S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Gastroenterology. 1991 Oct;101(4):954-61. doi: 10.1016/0016-5085(91)90721-v.
The role of capsaicin-sensitive afferent neurons in acid-induced HCO3- secretion was investigated in the duodenum of anesthetized rats. The proximal duodenum was perfused with saline (pH 4.5), the pH of perfusate and the transmucosal potential differences were continuously monitored, and HCO3- output was determined by pH change. Under these conditions, duodenal pH, potential difference, and HCO3- output were significantly increased in response to IV injection of prostaglandin E2 (300 micrograms/kg) and luminal acidification (10 mmol/L HCl, 10 minutes). These responses induced by luminal acid were significantly attenuated by SC pretreatment with indomethacin (5 mg/kg), preexposure of the mucosa to lidocaine (4%, 15 minutes), functional ablation of capsaicin-sensitive afferent neurons, or even prior application of capsaicin (6 mg/mL, 30 minutes) to the duodenum. Although capsaicin application by itself (0.3-6 mg/mL) produced a concentration-dependent increase of HCO3- output, this effect was significantly reduced by lidocaine, indomethacin, or chemical deafferentation and exhibited a tachyphylaxis after repeated application at a high concentration (6 mg/mL). Neither of these treatments significantly affected the HCO3- response induced by prostaglandin E2. It was concluded that stimulation of capsaicin-sensitive afferent neurons increased duodenal HCO3- secretion and that these neurons may be involved in the mechanism of HCO3- response induced by luminal acid in the duodenum.
在麻醉大鼠的十二指肠中研究了辣椒素敏感传入神经元在酸诱导的HCO₃⁻分泌中的作用。用生理盐水（pH 4.5）灌注十二指肠近端，持续监测灌注液的pH值和跨粘膜电位差，并通过pH变化测定HCO₃⁻输出量。在这些条件下，静脉注射前列腺素E2（300微克/千克）和腔内酸化（10毫摩尔/升盐酸，10分钟）后，十二指肠pH值、电位差和HCO₃⁻输出量显著增加。腔内酸诱导的这些反应被吲哚美辛（5毫克/千克）皮下预处理、粘膜预先暴露于利多卡因（4%，15分钟）、辣椒素敏感传入神经元的功能消融，甚至先前将辣椒素（6毫克/毫升，30分钟）应用于十二指肠显著减弱。尽管单独应用辣椒素（0.3 - 6毫克/毫升）会导致HCO₃⁻输出量呈浓度依赖性增加，但这种作用被利多卡因、吲哚美辛或化学去传入神经显著降低，并且在高浓度（6毫克/毫升）重复应用后出现快速耐受。这些处理均未显著影响前列腺素E2诱导的HCO₃⁻反应。得出的结论是，刺激辣椒素敏感传入神经元可增加十二指肠HCO₃⁻分泌，并且这些神经元可能参与十二指肠腔内酸诱导的HCO₃⁻反应机制。
