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Ghrelin inhibits autonomic response to gastric distension in rats by acting on vagal pathway.

ABSTRACT: Ghrelin is the only orexigenic peptide currently known and a potent prokinetic by promoting gastric motility but novel insights suggest that its role extends beyond satiety regulation. Whereas ghrelin was shown to provide somatic and colonic antinociception, its impact on gastric sensitivity is unknown even though stomach is a major ghrelin secreting tissue. Autonomic response to gastric mechanosensitivity was estimated by measuring blood pressure variation as a surrogate marker in response to gastric distension (GD) before and after ghrelin (or vehicle) administration. Involvement of spinal and vagal pathways in the ghrelin effect was studied by performing celiac ganglionectomy and subdiaphragmatic vagotomy respectively and by evaluating the expression of phosphorylated extracellular-regulated kinase 1/2 (p-ERK1/2) in dorsal root and nodose ganglia. Finally the phenotype of Ghrelin receptor expressing neurons within the nodose ganglia was determined by in situ hybridization and immunofluorescence. Ghrelin reduced blood pressure variation in response to GD except in vagotomized rats. Phosphorylated-ERK1/2 levels indicated that ghrelin reduced neuronal activation induced by GD in nodose ganglion. The effect of ghrelin on gastric mechanosensitivity was abolished by pre-treatment with antagonist [D-Lys³]-GHRP-6 (0.3?mg/kg i.v.). Immunofluorescence staining highlights the colocalization of Ghrelin receptor with ASIC3 and TRPV1 within gastric neurons of nodose ganglion. Ghrelin administration reduced autonomic response to gastric distension. This effect likely involved the Ghrelin receptor and vagal pathways.

SUBMITTER: Meleine M

PROVIDER: S-EPMC7305309 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Ghrelin inhibits autonomic response to gastric distension in rats by acting on vagal pathway.

Meleine Mathieu M Mounien Lourdes L Atmani Karim K Ouelaa Wassila W Bôle-Feysot Christine C Guérin Charlène C Depoortere Inge I Gourcerol Guillaume G

Scientific reports 20200619 1

Ghrelin is the only orexigenic peptide currently known and a potent prokinetic by promoting gastric motility but novel insights suggest that its role extends beyond satiety regulation. Whereas ghrelin was shown to provide somatic and colonic antinociception, its impact on gastric sensitivity is unknown even though stomach is a major ghrelin secreting tissue. Autonomic response to gastric mechanosensitivity was estimated by measuring blood pressure variation as a surrogate marker in response to g ...[more]

PMID: 32561800

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Project description:BACKGROUND:This study aimed to evaluate effects of electric vagal nerve stimulation on early postoperation cognitive dysfunction in aged rats. METHODS:A total of 33 male Sprague Dawley rats were selected and assigned randomly to three groups, control group (C, n?=?10), splenectomy group (S, n?=?10) and splenectomy+vagal nerve stimulation group (SV, n?=?13). Behavior and memory of rats were evaluated by Open Field Test and Morris Water Maze. Levels of TNF-?, IL-6 and IL-10 in serum were measured by ELISA. The level of TNF-? protein in hippocampus was assessed by Western blotting. rt-PCR was used to detect mRNA expression of NF-?B in hippocampus. RESULTS:During anesthesia/operation, vital life signs of rats were stable. In SV group, vagal nerve stimulation decreased heart rate lower than 10% of basic level and kept it at a stable range by regulating stimulation intensity. After stimulation stop, heart rate returned to the basic level again. This indicated that the model of vagal nerve stimulation was successful. Serum levels of TNF-? and IL-6 increased by the operation/anesthesia, but they decreased with vagal nerve stimulation (all P?<?0.05). TNF-? protein and mRNA expression of NF-?B in hippocampus were also eliminated by vagal nerve stimulation compared to S group (P?<?0.05). Results of Morris Water Maze showed escape latency of postoperation in S group was significantly longer than C group (P?<?0.05), and times of crossing platform in S group was lower than that of C group (P?<?0.05). Although escape latency of postopration in SV group was shorter than that of S group, there was no significant difference between two groups. Meanwhile there were no significant differences of behavior test in Open Field test between three groups, although vagal nerve stimulation improved partly active explore behavior compared to S group. CONCLUSION:The inflammation caused by operation and general anesthesia was an important reason of early postoperation cognitive dysfunction, and electric vagal nerve stimulation could inhibit the inflammation. Meanwhile, vagal nerve stimulation could ameliorate early postoperation cognitive dysfunction partly, but its protective effects were not enough and should be studied and improved in future.

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Ghrelin inhibits autonomic response to gastric distension in rats by acting on vagal pathway.

Publications

Ghrelin inhibits autonomic response to gastric distension in rats by acting on vagal pathway.

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