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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.
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Submitted on : Thursday, July 2, 2020 - 9:29:55 AM
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Mathieu Meleine, Lourdes Mounien, Karim Atmani, Wassila Ouelaa, Christine Bôle-Feysot, et al.. Ghrelin inhibits autonomic response to gastric distension in rats by acting on vagal pathway. Scientific Reports, Nature Publishing Group, 2020, 10 (1), pp.9986. ⟨10.1038/s41598-020-67053-y⟩. ⟨inserm-02887200⟩



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