Fourth ventricular administration of ghrelin induces relaxation of the proximal stomach in the rat

Abstract

appetite; vagus; fundus; stomach; medulla GHRELIN IS A RECENTLY IDENTIFIED endogenous ligand for growth hormone secretagogue receptor (GHS-R) and was originally isolated from the stomach (19). In addition to GH-releasing activity, ghrelin has an orexigenic (appetite-enhancing) effect. This is very reasonable, since the blood ghrelin level rose sharply just before onset of the dark phase, and the stomach ghrelin level was high during fasting in rats (30). Ghrelin has been shown to be present not only in the stomach but also in the hypothalamus, and it participates in the regulation of food intake itself and feeding-related phenomena through the peripheral and central nervous system (5, 25). Since feeding is closely related to digestive function, the effects of orexigenic peptides on gastric acid secretion, bile secretion, and gastric motility have been well investigated (3,10,15,18,20,24,29,35). Orexigenic peptides generally stimulate gastric acid secretion (23,24,33) and phasic contractions of the distal stomach (3,15,20,23), which enhance the ability to churn the gastric contents to accelerate gastric emptying; these gastric functions are particularly important for digestion. Accommodation of food is also important for smooth digestion, and impaired accommodation is thought to be one of the factors inducing meal-related symptoms, such as functional dyspepsia (31). The proximal region of the stomach, which serves as a reservoir, relaxes to accommodate food and fluid during swallowing (2, 17). Our previous studies revealed that fourth ventricular administration (and/or intramedullary injections) of orexin-A and neuropeptide Y (NPY), which are well-known orexigenic peptides, induced relaxation of the proximal stomach to facilitate the reservoir function of the stomach (15, 18).Ghrelin, as well as other orexigenic peptides, controls gastric functions. Intravenous administration of ghrelin stimulates gastric acid secretion and gastric motility in rats (23). Central and peripheral administration of ghrelin induced fasted motor activity of the gastrointestinal tract in rats (8). Histological study confirmed GHS-R mRNA expression in several hypothalamic nuclei, many of which have long been recognized as playing roles in body weight and food intake in rats and mice (37). In addition, GHS-R mRNA has also been found in the dorsal vagal complex (DVC), including the area postrema (AP), nucleus of the solitary tract (NST) and dorsal motor nucleus of the vagus (DMV). Immunohistochemical study revealed that GHS-R was expressed in the NST and DMV in rats (22). Microinjection of ghrelin into the DVC facilitated food intake (7). Since the DVC is the center for controlling gastric motility, it is plausible that ghrelin induces relaxation of the proximal stomach, as well as other orexigenic peptides, as shown in our previous studies (15,18). Additionally, recent studies revealed that the intermediate and caudal DMV contain different groups of preganglionic neurons (21, 36). It is well known that the caudal part of the DMV is involv...

Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

“…To test this hypothesis, we used a selective GHSR antagonist [D-lys 3 ]-GHRP-6 to abolish the actions of ghrelin. We adopted a 37.5-fold dose of ghrelin administered which was shown to effectively blockage the GHSR-1a [22]. In our study, [D-lys 3 ]-GHRP-6 disabled the effects of ghrelin, indicating that ghrelin exerted a protective effect on barrier dysfunction through the GHSR-1a pathway.…”

Desacyl ghrelin prevents doxorubicin-induced myocardial fibrosis and apoptosis via the GHSR-independent pathway

“…In this study, the previously reported dosage of 100 g/kg body wt of desacyl ghrelin injected twice daily was adopted (33,38). We adopted a dosage of 3.75 mg/kg [D-Lys3]-GHRP-6 (37.5-fold dose of desacyl ghrelin), which was shown to effectively abolish the ghrelin-GHSR signaling (25). Mice in the DOX ϩ DAG ϩ [D-Lys3]-GHRP-6 group were administrated with [D-Lys3]-GHRP-6 immediately before desacyl ghrelin injection.…”

Ghrelin increases vagally mediated gastric activity by central sites of action

“…Ghrelin secretion exerts profound stimulatory effects upon gastric motility and acid secretion as well as food intake and energy metabolism 6–10 . This stimulatory effect has been demonstrated in both fed and fasted states 11,12 .…”