Role of central ghrelin in the gastric accommodation and reflex swallowing

Ghrelin is an endogenous ligand for growth hormone secretagogue receptor (GHS-R), and was originally isolated from the stomach. In addition to GH-releasing activity, ghrelin has an orexigenic (appetite-enhancing) effect. This is rational, since the blood and stomach ghrelin levels are high during fasting in rats. Ghrelin has been shown to be present not only in the stomach but also in the hypothalamus, and participates in the regulation of food intake itself and feeding-related phenomena through the peripheral and central nervous system. Although the hypothalamic nuclei have an essential role in feeding, the nuclei in the caudal brainstem modify food intake in response to ghrelin. This region has a substantial role in swallowing, gastric motility and gastric secretion. Since swallowing and gastric accommodation are important for smooth digestion and are involved in the sequence of events, we examined the central effect of ghrelin on reflex swallowing and the reservoir function of the stomach in urethane-chloralose anaesthetized rats. Fourth ventricular administration of ghrelin but not a vehicle induced relaxation of the proximal stomach lasting for more than 30 min. Administration of ghrelin with a growth hormone secretagogue receptor antagonist ([D-Lys3] GHRP-6) into the fourth ventricle did not induce a significant change in intragastric pressure. Bilateral sectioning of the vagi at the cervical level abolished the relaxation induced by the administration of ghrelin into the fourth ventricle. Microinjections of ghrelin into the caudal part of the dorsal vagal complex (DVC) induced obvious relaxation of the proximal stomach. These results revealed that ghrelin induced relaxation in the proximal stomach via GHS-R situated in the caudal DVC. Fasting is usually followed by feeding; therefore, gastric relaxation achieved by the actions of orexigenic neuropeptides, which are released by hunger, to enhance the easy accommodation of food is rational. Since gastric relaxation is closely related to swallowing, we further examined the effect of ghrelin on reflex swallowing in anaesthetized rats. Fourth ventricular administration of ghrelin significantly decreased swallowing frequency during electrical stimulation of the central cut end of the superior laryngeal nerve (SLN stimulation). The administration of ghrelin with [D-Lys3] GHRP-6 did not change swallowing frequency during SLN stimulation. Since microinjection of ghrelin into the vicinity of the solitary tract inhibited swallowing frequency induced by SLN stimulation, ghrelin inhibited reflex swallowing by modifying neural activities of the dorsal medulla where the swallowing center is housed. In conclusion, central ghrelin regulates extensive autonomic phenomena associated with food intake by way of the caudal brainstem.