人幽门括约肌中血管活性肠肽和P物质的调节

Regulation of vasoactive intestinal peptide and substance P in the human pyloric sphincter.

作者信息

Tomita Ryouichi

机构信息

First Department of Surgery, Nihon University School of Medicine, Tokyo 173-0032, Japan.

出版信息

Hepatogastroenterology. 2009 Sep-Oct;56(94-95):1403-6.

PMID:19950799

Abstract

BACKGROUND/AIMS: Brain-gut hormones (i.e., neuropeptides) such as vasoactive intestinal peptide (VIP) and substance P (SP) have been shown to exist in the enteric nervous system (ENS) of the pyloric sphincter (PS) in studies of immunohistochemistry. To clarify the role of neuropeptides in the ENS of the normal human PS, we investigated the enteric nerve responses to VIP and SP in normal human PS specimens in vitro.

METHODOLOGY

Normal human PS specimens derived from 45 patients with early gastric cancer (35 men and 10 women aged from 44 to 65 years, average 57.4 years) were used. A total of 120 PS muscle strips were made from 45 PS. A mechanographic technique was used to evaluate in vitro muscle strip responses to VIP and SP before and after treatment with various autonomic nerve blockers.

RESULTS

Responses to VIP and SP after blockade of the adrenergic and cholinergic nerves: Relaxation was elicited by VIP in 41.7% at 1 x 10(-8), 62.5% at 1 x 10(-7), and 83.3% at 1 x 10(-6) g/ml. Differences were noted in the percentages showing relaxation between 1 x 10(-8) and 1 x 10(-7) 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 = 0.0012, p < 0.0001, p = 0.0002, respectively). Contraction was elicited by administration of by SP in 31.7% at 1 x 10(-8), 58.3% at 1 x 10(-7), and 79.2% at 1 x 10(-6) g/ml, respectively. Differences were noted in the percentages showing contraction between 1 x 10(-8) and 1 x 10(-7) 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 = 0.0001, p < 0.0001, p = 0.0004, respectively). VIP caused relaxation and substance P caused contraction of the PS in a concentration-dependent manner. Response to VIP and SP at 1 x 10(-6) g/ml after blockade of the ENS by tetrodotoxin (TTX): The relaxation to VIP and contraction to SP following administration of TTX were weaker than after blockade of the adrenergic and cholinergic nerves. In the normal human PS, VIP and SP may act both via NANC nerves and directly on the muscle strips.

CONCLUSIONS

Relaxation reaction via VIP nerves and contraction via SP nerves might be involved in regulation of ENS in the normal human PS.

摘要

背景/目的：免疫组化研究显示，血管活性肠肽（VIP）和P物质（SP）等脑肠肽（即神经肽）存在于幽门括约肌（PS）的肠神经系统（ENS）中。为阐明神经肽在正常人体PS的ENS中的作用，我们在体外研究了正常人体PS标本对VIP和SP的肠神经反应。

方法

使用来自45例早期胃癌患者（35名男性和10名女性，年龄44至65岁，平均57.4岁）的正常人体PS标本。从45个PS中制作了总共120条PS肌肉条。采用机械记录技术评估在使用各种自主神经阻滞剂治疗前后体外肌肉条对VIP和SP的反应。

结果

肾上腺素能和胆碱能神经阻断后对VIP和SP的反应：VIP在1×10⁻⁸g/ml时引起41.7%的松弛，在1×10⁻⁷g/ml时引起62.5%的松弛，在1×10⁻⁶g/ml时引起83.3%的松弛。在1×10⁻⁸与1×10⁻⁷g/ml之间、1×10⁻⁸与1×10⁻⁶g/ml之间以及1×10⁻⁷与1×10⁻⁶g/ml之间显示松弛的百分比存在差异（分别为p = 0.0012、p < 0.0001、p = 0.0002）。SP在1×10⁻⁸g/ml时引起31.7%的收缩，在1×10⁻⁷g/ml时引起58.3%的收缩，在1×10⁻⁶g/ml时引起79.2%的收缩。在1×10⁻⁸与1×10⁻⁷g/ml之间、1×10⁻⁸与1×10⁻⁶g/ml之间以及1×10⁻⁷与1×10⁻⁶g/ml之间显示收缩的百分比存在差异（分别为p = 0.0001、p < 0.0001、p = 0.0004）。VIP以浓度依赖的方式引起PS松弛，P物质引起PS收缩。河豚毒素（TTX）阻断ENS后对1×10⁻⁶g/ml的VIP和SP的反应：给予TTX后对VIP的松弛反应和对SP的收缩反应比肾上腺素能和胆碱能神经阻断后弱。在正常人体PS中，VIP和SP可能通过非肾上腺素能非胆碱能（NANC）神经起作用，并直接作用于肌肉条。