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氮能神经通路是 DA-9701 对大鼠胃底舒张作用的主要机制。

Nitrergic Pathway Is the Major Mechanism for the Effect of DA-9701 on the Rat Gastric Fundus Relaxation.

机构信息

Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.

Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

J Neurogastroenterol Motil. 2014 Jul 31;20(3):318-25. doi: 10.5056/jnm13098.

DOI:10.5056/jnm13098
PMID:24920748
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4102157/
Abstract

BACKGROUND/AIMS: DA-9701 significantly improved gastric accommodation by increasing the postprandial gastric volume. In this study, we investigated how DA-9701 affects the rat gastric fundus relaxation.

METHODS

Gastric fundus muscle strips (9 longitudinal and 7 circular muscles) were obtained from rats. Electrical field stimulation (EFS) was performed at various frequencies (1, 5, 10 and 20 Hz) and train durations (1, 5, 10 and 20 seconds) to select optimal condition for experiments. Isometric force measurements were performed in response to EFS. Peak and nadir were observed during the first 1 minute after initiation of EFS in control state and after sequential addition of atropine (1 μM), DA-9701 (0.5, 5, 25 and 50 μg), N-nitro-L-arginine (L-NNA, 100 μM), MRS2500 (1 μM) and tetrodotoxin (TTX, 1 μM) to the organ bath.

RESULTS

The optimal frequency and duration of EFS to evoke nerve-mediated relaxation was determined as 5 Hz for 10 seconds. Addition of L-NNA in the presence of atropine and DA-9701 (50 μg) decreased nadir by inhibiting relaxation from -0.054 ± 0.021 g to -0.022 ± 0.015 g (P = 0.026) in longitudinal muscles. However, subsequent application of MRS2500 in the presence of atropine, DA-9701 (50 μg) and L-NNA did not affect nadir. In circular muscles, subsequent addition of L-NNA and MRS2500 in the presence of atropine and DA-9701 (50 μg) did not show significant change of nadir.

CONCLUSIONS

Our data suggest that the effect of DA-9701 on the rat gastric fundus relaxation is mainly mediated by nitrergic rather than purinergic pathway.

摘要

背景/目的：DA-9701 通过增加餐后胃容量显著改善胃容纳性。在这项研究中，我们研究了 DA-9701 如何影响大鼠胃底松弛。

方法

从大鼠中获得胃底肌条（9 条纵向和 7 条环形肌）。对电刺激（EFS）以不同频率（1、5、10 和 20 Hz）和刺激时长（1、5、10 和 20 秒）进行刺激，以选择实验的最佳条件。对 EFS 响应进行等长力测量。在对照状态下以及在向器官浴中依次添加阿托品（1 μM）、DA-9701（0.5、5、25 和 50 μg）、N-硝基-L-精氨酸（L-NNA，100 μM）、MRS2500（1 μM）和河豚毒素（TTX，1 μM）之后的第 1 分钟观察到峰和谷。

结果

确定诱发神经介导松弛的 EFS 的最佳频率和时长为 5 Hz 持续 10 秒。在存在阿托品和 DA-9701（50 μg）的情况下添加 L-NNA 会抑制松弛，使纵向肌中的谷值从-0.054±0.021 g 降低至-0.022±0.015 g（P=0.026）。然而，在存在阿托品、DA-9701（50 μg）和 L-NNA 的情况下，随后应用 MRS2500 对谷值没有影响。在环形肌中，在存在阿托品、DA-9701（50 μg）和 L-NNA 的情况下，随后添加 L-NNA 和 MRS2500 并没有显著改变谷值。

结论

我们的数据表明，DA-9701 对大鼠胃底松弛的影响主要是通过 nitrergic 途径而不是 purinergic 途径介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5853/4102157/a53841f9fe1a/jnm-20-318f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5853/4102157/75f486d46201/jnm-20-318f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5853/4102157/755addc45b6a/jnm-20-318f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5853/4102157/ce9e834393f5/jnm-20-318f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5853/4102157/a66a9aa79f13/jnm-20-318f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5853/4102157/a53841f9fe1a/jnm-20-318f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5853/4102157/75f486d46201/jnm-20-318f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5853/4102157/755addc45b6a/jnm-20-318f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5853/4102157/ce9e834393f5/jnm-20-318f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5853/4102157/a66a9aa79f13/jnm-20-318f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5853/4102157/a53841f9fe1a/jnm-20-318f5.jpg

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