Ishiguro Mitsunori, Nakayama Kiyomi, Nakamura Shiro, Mochizuki Ayako, Dantsuji Masanori, Ihara Yoshiaki, Inoue Tomio
Department of Oral Physiology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan; Department of Special Needs Dentistry, Division of Oral Rehabilitation Medicine, Showa University School of Dentistry, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan.
Department of Oral Physiology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Brain Res Bull. 2023 Jan;192:62-69. doi: 10.1016/j.brainresbull.2022.11.006. Epub 2022 Nov 9.
Ghrelin, a peripheral peptide produced in the stomach, is involved in the neural networks that control food intake. Alterations in motor components, such as swallowing, are believed to be significant in the regulation food intake by orexigenic signals. However, there has been no detailed investigation of the relationship between ghrelin and swallowing activities induced in motor nerves innervating the pharyngeal and laryngeal muscles. In this study, we examined the effects of ghrelin administration on swallowing motor activity in arterially perfused rats. Injection of distilled water (0.5 ml) into the oral cavity or electrical stimulation of the superior laryngeal nerve evoked swallowing motor activity in the cervical vagus nerve. Administration of ghrelin (6 nM), but not des-acylated ghrelin (6 nM), into the perfusate increased the peak burst amplitude and burst duration, and shortened the first burst interval of water injection-induced swallowing. These ghrelin-induced changes in swallowing motor activity were blocked by the administration of JMV2959 (6 µM), a growth hormone secretagogue receptor antagonist. In preparations in which the hypothalamus was removed, ghrelin had no effect on swallowing motor activity. Furthermore, ghrelin-induced changes were counteracted by the administration of BIBO3304 (1 µM) or L-152,804 (1 µM), antagonists of neuropeptide Y Y1 and Y5 receptors, respectively, which are essential for ghrelin-induced enhancement of food intake. Ghrelin also increased the peak burst amplitude and burst duration of the swallowing motor activity evoked by electrical stimulation of the superior laryngeal nerve, although the effects of ghrelin on the number of swallowing bursts and burst intervals varied with stimulus intensity. These results suggest that ghrelin enhances the magnitude and frequency of bursts of swallowing motor activity by acting via the hypothalamic neural network, and that neuropeptide Y Y1 and Y5 receptors are involved in this enhancement.
胃饥饿素是一种在胃中产生的外周肽，参与控制食物摄入的神经网络。吞咽等运动成分的改变被认为在食欲信号调节食物摄入中起重要作用。然而，对于胃饥饿素与支配咽喉肌肉的运动神经中诱导的吞咽活动之间的关系，尚未进行详细研究。在本研究中，我们检测了给予胃饥饿素对动脉灌注大鼠吞咽运动活动的影响。向口腔注射蒸馏水（0.5毫升）或电刺激喉上神经可诱发颈迷走神经中的吞咽运动活动。向灌注液中给予胃饥饿素（6纳摩尔）而非去酰基胃饥饿素（6纳摩尔），可增加注水诱导吞咽的峰值爆发幅度和爆发持续时间，并缩短首次爆发间隔。这些胃饥饿素诱导的吞咽运动活动变化可被生长激素促分泌素受体拮抗剂JMV2959（6微摩尔）所阻断。在去除下丘脑的制备物中，胃饥饿素对吞咽运动活动无影响。此外，分别给予神经肽Y Y1受体拮抗剂BIBO3304（1微摩尔）或Y5受体拮抗剂L-152,804（1微摩尔）可抵消胃饥饿素诱导的变化，这两种受体对于胃饥饿素诱导的食物摄入量增加至关重要。胃饥饿素还增加了电刺激喉上神经诱发的吞咽运动活动的峰值爆发幅度和爆发持续时间，尽管胃饥饿素对吞咽爆发次数和爆发间隔的影响随刺激强度而变化。这些结果表明，胃饥饿素通过下丘脑神经网络起作用，增强吞咽运动活动爆发的幅度和频率，并且神经肽Y Y1和Y5受体参与了这种增强作用。
