Tomita Ryouichi, Igarashi Seigo, Tanjoh Katuhisa, Fujisaki Shigeru
Department of Surgery, Nippon Dental University School of Dentistry at Tokyo Nippon Dental University Hospital, Japan.
Hepatogastroenterology. 2005 Sep-Oct;52(65):1459-62.
BACKGROUND/AIMS: Glicentin (GL) is known as an inhibitory factor for alimentary tract movement and the possibility that GL may be a neuromodulator of the non-adrenergic non-cholinergic (NANC) inhibitory nerves has been reported from animal experiments. Since sufficient amounts of GL have not been available for the physiological studies, there is no report concerning the effects of GL on the enteric nervous system in the normal human small intestine. Recently synthesized recombinant human GL (rh-GL) has become available to study the physiological action of GL. To clarify the physiological significance of GL in the normal human small intestine, enteric nervous responses to GL in the normal small bowel were investigated.
Normal jejunal muscle strips (thirty-two preparations) derived from patients who underwent jejunal resection for advanced gastric cancers (14 cases) were used. The subjects consisted of 10 men and 4 women, aged from 48 to 66 years with a mean age of 59.9 years. A mechanographic technique was used to evaluate the in vitro jejunal muscle responses to GL (recombinant human GL; rh-GL) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. All muscle strips used in this study reacted to the electrical field stimulation (EFS), which was thus suitable for stimulation of enteric nervous system.
In experiment I (the responses to rh-GL after blockade of the adrenergic and cholinergic nerves) the inhibition reaction ofjejunal contraction movement was concentration-dependent; 0% at 1 x 10(-9) g/mL, 6.3% at 1 x 10(-8) g/mL, 12.5% at 1 x 10(-7) g/mL, and 43.8% at 1 x 10(-6) g/mL. The remaining muscle strips demonstrated no reaction to rh-GL. In addition, significant differences were noted between 1 x 10(-9) and 1 x 10(-6) g/mL, between 1 x 10(-8) and 1 x 10(-6) g/mL, and between 1 x 10(-7) and 1 x 10(-6) g/mL (P=0.0005, P=0.0066, P=0.0359, respectively). Rh-GL concentration-dependently inhibited a contraction reaction after blockade of the adrenergic and cholinergic nerves. In experiment II (responses to rh-GL following administration of tetrodotoxin) tetrodotoxin did not block the inhibition of contraction reaction in response to rh-GL in the human jejunum. Inhibition reaction of contraction movement was seen in the jejunal muscle strips, as in experiment I.
GL plays an important role in the regulating inhibition of the contraction reaction in normal human jejunum via NANC nerves, and has a direct action on the jejunal muscle receptor.
背景/目的：甘丙肽（GL）是已知的消化道运动抑制因子，动物实验已报道GL可能是非肾上腺素能非胆碱能（NANC）抑制性神经的神经调节剂。由于尚未获得足够量的GL用于生理学研究，因此尚无关于GL对正常人类小肠肠神经系统作用的报道。最近合成的重组人GL（rh - GL）已可用于研究GL的生理作用。为阐明GL在正常人类小肠中的生理意义，研究了正常小肠对GL的肠神经反应。
使用来自因进展期胃癌接受空肠切除术患者（14例）的正常空肠肌条（32份标本）。受试者包括10名男性和4名女性，年龄在48至66岁之间，平均年龄59.9岁。采用机械记录技术评估在用各种自主神经阻滞剂处理前后，空肠肌对肾上腺素能和胆碱能神经的GL（重组人GL；rh - GL）的体外反应。本研究中使用的所有肌条对电场刺激（EFS）均有反应，因此适合刺激肠神经系统。
在实验I（肾上腺素能和胆碱能神经阻断后对rh - GL的反应）中，空肠收缩运动的抑制反应呈浓度依赖性；1×10⁻⁹ g/mL时为0%，1×10⁻⁸ g/mL时为6.3%，1×10⁻⁷ g/mL时为12.5%，1×10⁻⁶ g/mL时为43.8%。其余肌条对rh - GL无反应。此外，在1×10⁻⁹与1×10⁻⁶ g/mL之间、1×10⁻⁸与1×10⁻⁶ g/mL之间以及1×10⁻⁷与1×10⁻⁶ g/mL之间观察到显著差异（分别为P = 0.0005、P = 0.0066、P = 0.0359）。rh - GL浓度依赖性地抑制了肾上腺素能和胆碱能神经阻断后的收缩反应。在实验II（给予河豚毒素后对rh - GL的反应）中，河豚毒素并未阻断人空肠中对rh - GL的收缩反应抑制。与实验I一样，在空肠肌条中观察到收缩运动的抑制反应。
GL通过NANC神经在调节正常人类空肠收缩反应的抑制中起重要作用，并且对空肠肌受体有直接作用。
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