Takeuchi K, Ohuchi T, Matsumoto J, Okabe S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
J Clin Gastroenterol. 1993;17 Suppl 1:S33-9. doi: 10.1097/00004836-199312001-00009.
We investigated the role of capsaicin-sensitive sensory neurons in regulation of gastroduodenal HCO3- secretion in anesthetized rats. The stomach (under acid inhibition by omeprazole 60 mg/kg i.p.) or the duodenum was perfused with saline (pH 4.5) and HCO3- output was determined by pH change in the perfusate. Both the duodenum and stomach responded to prostaglandin E2 (PGE2; 300 micrograms/kg i.v.) or luminal acid by a significant increase in pH and HCO3- output. These tissues also responded to luminal application of capsaicin (0.3-6 mg/ml for 30 min), resulting in a significant increase of pH and HCO3- output in a concentration-related manner. The HCO3- stimulatory action of capsaicin was markedly attenuated by functional ablation of capsaicin-sensitive sensory neurons, significantly mitigated by indomethacin, and exhibited tachyphylaxis after repeated application at a high concentration. The acid-induced pH and HCO3- responses were also significantly mitigated by sensory deafferentation and by indomethacin, whereas those induced by PGE2 remained unaffected. In addition, defunctionalization of these sensory nerves resulted in macroscopically visible damage in the duodenum when acid secretion was concomitantly stimulated by histamine. We conclude that capsaicin-sensitive sensory neurons may be involved in the regulatory mechanism of gastroduodenal HCO3- secretion and contribute to protection of the mucosa against acid. Endogenous PGs may be involved in the HCO3- stimulatory action mediated by capsaicin-sensitive sensory neurons.
我们研究了辣椒素敏感感觉神经元在麻醉大鼠胃十二指肠HCO₃⁻分泌调节中的作用。用生理盐水（pH 4.5）灌注胃（在静脉注射60 mg/kg奥美拉唑抑制胃酸的情况下）或十二指肠，并通过灌流液中的pH变化来测定HCO₃⁻的输出量。十二指肠和胃对前列腺素E₂（PGE₂；静脉注射300微克/千克）或腔内酸刺激的反应均表现为pH值和HCO₃⁻输出量显著增加。这些组织对腔内应用辣椒素（0.3 - 6毫克/毫升，持续30分钟）也有反应，导致pH值和HCO₃⁻输出量以浓度相关的方式显著增加。辣椒素对HCO₃⁻的刺激作用在辣椒素敏感感觉神经元功能缺失后明显减弱，吲哚美辛可显著减轻该作用，且在高浓度重复应用后出现快速耐受。感觉神经切断和吲哚美辛也可显著减轻酸诱导的pH值和HCO₃⁻反应，而PGE₂诱导的反应则不受影响。此外，当组胺同时刺激胃酸分泌时，这些感觉神经功能缺失会导致十二指肠出现肉眼可见的损伤。我们得出结论，辣椒素敏感感觉神经元可能参与胃十二指肠HCO₃⁻分泌的调节机制，并有助于保护黏膜免受酸的侵害。内源性前列腺素可能参与辣椒素敏感感觉神经元介导的HCO₃⁻刺激作用。
