Involvement of ghrelin in the regulation of swallowing motor activity in an arterially perfused rat preparation

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.