Kobashi Motoi, Mizutani Satoshi, Fujita Masako, Mitoh Yoshihiro, Shimatani Yuichi, Matsuo Ryuji
Department of Oral Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Japan.
Department of Oral Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Japan.
Brain Res. 2017 Sep 15;1671:26-32. doi: 10.1016/j.brainres.2017.07.004. Epub 2017 Jul 8.
The effects of glucagon like peptide-1 (GLP-1) on reflex swallowing were examined using anaesthetized rats. GLP-1 was injected into the dorsal vagal complex (DVC) using glass micropipettes. Swallowing was induced by repeated electrical stimulation of the central cut end of the superior laryngeal nerve (SLN) and was identified by the electromyogram lead penetrated in the mylohyoide muscle through bipolar electrodes. Microinjection of GLP-1 into the medial DVC (M-DVC) increased the frequency of swallowing during the electrical stimulation of the SLN and extended the latency of the first swallowing. Microinjection of GLP-1 into the lateral DVC (L-DVC) did not change the frequency of swallowing or the latency of the first swallowing. Neither the injection of vehicle into the M-DVC nor L-DVC affected swallowing frequency. Pre-injection of exendin (5-39), a GLP-1 receptor antagonist, attenuated the degree of suppression of swallowing frequency induced by the administration of GLP-1 in addition to shortening the latency of the first swallowing. To identify the effective site of GLP-1, lesion experiments were performed. Electrical lesion of the commissural part of the NTS (cNTS) and the vacuum removal of the area postrema (AP) did not affect the inhibition of reflex swallowing induced by the injection of GLP-1 into the M-DVC. Electrical lesion of the medial nucleus of the NTS (mNTS) and its vicinity abolished the inhibitory effects of swallowing induced by the injection of GLP-1. These results suggest that GLP-1 inhibits reflex swallowing via the mNTS in the dorsal medulla.
利用麻醉大鼠研究了胰高血糖素样肽-1(GLP-1)对反射性吞咽的影响。使用玻璃微量移液器将GLP-1注入迷走神经背侧复合体(DVC)。通过反复电刺激喉上神经(SLN)的中枢切断端诱导吞咽,并通过双极电极穿透颏舌骨肌的肌电图导联来识别吞咽。向内侧DVC(M-DVC)微量注射GLP-1可增加SLN电刺激期间的吞咽频率,并延长首次吞咽的潜伏期。向外侧DVC(L-DVC)微量注射GLP-1不会改变吞咽频率或首次吞咽的潜伏期。向M-DVC或L-DVC注射溶媒均不影响吞咽频率。预先注射GLP-1受体拮抗剂艾塞那肽(5-39),除了缩短首次吞咽的潜伏期外,还减弱了GLP-1给药引起的吞咽频率抑制程度。为了确定GLP-1的有效作用部位,进行了损伤实验。孤束核(NTS)连合部(cNTS)的电损伤和最后区(AP)的抽空均不影响向M-DVC注射GLP-1引起的反射性吞咽抑制。NTS内侧核(mNTS)及其附近区域的电损伤消除了注射GLP-1引起的吞咽抑制作用。这些结果表明,GLP-1通过延髓背侧的mNTS抑制反射性吞咽。