Glucagon-like peptide-2 (GLP-2) has been reported to indirectly relax gastric smooth muscle. In the present study we investigated, through a combined mechanical and immunohistochemical approach, whether GLP-2 interferes with the electrical field stimulation (EFS)-induced vipergic relaxant responses and the mechanism through which it occurs. For functional experiments, strips from the mouse gastric fundus were mounted in organ baths for isometric recording of the mechanical activity. Vasoactive intestinal peptide (VIP) immunoreactivity in GLP-2 exposed specimens was also evaluated by immunohistochemistry. In carbachol pre-contracted strips, GLP-2 (20 nM) evoked a tetrodotoxin (TTX)-sensitive relaxation, similar in shape to the TTX-insensitive of 100 nM VIP. In the presence of GLP-2, VIP had no longer effects and no more response to GLP-2 was observed following VIP receptor saturation. EFS (4-16 Hz) induced a fast relaxant response followed, at the higher stimulation frequencies (≥ 8 Hz), by a slow one. This latter was abolished either by GLP-2 or VIP receptor saturation as well as by the VIP receptor antagonist, VIP 6-28 (10 μM). A decrease of VIP-immunoreactive nerve structures in the GLP-2 exposed specimens was observed. These results suggest that, in the mouse gastric fundus, GLP-2 influences the EFS-induced slow relaxant response by promoting neuronal VIP release.

中文翻译：

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胰高血糖素样肽 2 通过 VIP 释放干扰小鼠胃条中神经诱导的松弛反应

据报道，胰高血糖素样肽 2 (GLP-2) 可间接松弛胃平滑肌。在本研究中，我们通过机械和免疫组织化学相结合的方法调查了 GLP-2 是否干扰电场刺激 (EFS) 诱导的蝰蛇神经松弛反应及其发生的机制。对于功能实验，将小鼠胃底的条带安装在器官浴中以等距记录机械活动。还通过免疫组织化学评估了 GLP-2 暴露样本中的血管活性肠肽 (VIP) 免疫反应性。在氨甲酰胆碱预收缩条中，GLP-2 (20 nM) 引起河豚毒素 (TTX) 敏感的松弛，形状类似于 100 nM VIP 的 TTX 不敏感。在 GLP-2 存在下，VIP 不再有影响，并且在 VIP 受体饱和后不再观察到对 GLP-2 的反应。EFS (4-16 Hz) 诱导快速松弛反应，随后在较高刺激频率 (≥ 8 Hz) 下缓慢响应。后者被 GLP-2 或 VIP 受体饱和以及 VIP 受体拮抗剂 VIP 6-28 (10 μM) 消除。观察到 GLP-2 暴露样本中 VIP 免疫反应性神经结构的减少。这些结果表明，在小鼠胃底，GLP-2 通过促进神经元 VIP 释放来影响 EFS 诱导的缓慢松弛反应。后者被 GLP-2 或 VIP 受体饱和以及 VIP 受体拮抗剂 VIP 6-28 (10 μM) 消除。观察到 GLP-2 暴露样本中 VIP 免疫反应性神经结构的减少。这些结果表明，在小鼠胃底，GLP-2 通过促进神经元 VIP 释放来影响 EFS 诱导的缓慢松弛反应。后者被 GLP-2 或 VIP 受体饱和以及 VIP 受体拮抗剂 VIP 6-28 (10 μM) 消除。观察到 GLP-2 暴露样本中 VIP 免疫反应性神经结构的减少。这些结果表明，在小鼠胃底，GLP-2 通过促进神经元 VIP 释放来影响 EFS 诱导的缓慢松弛反应。