title: Somatostatin stimulates intestinal NHE8 expression via p38 MAPK pathway.
abstract: Diarrhea is a common manifestation of gastrointestinal disorders. Diarrhea-induced losses of fluid and electrolyte could lead to dehydration and electrolyte imbalances, resulting in significant morbidity and mortality, especially in children living in developing countries. Somatostatin, a peptide hormone secreted by D-cells, plays an important role in regulating motility and intestinal Na(+) absorption. Although octreotide, a somatostatin analog, is used to treat diarrhea, its mechanisms of action are unclear. Here we showed that octreotide increased brush-border membrane Na(+)/H(+) exchanger 8 (NHE8) expression in the small intestine to the exclusion of other NHEs that participate in Na(+) absorption. The same effect also occurred in human intestinal cells (Caco-2). We found that the increase of NHE8 expression by somatostatin required p38 mitogen-activated protein kinase (MAPK) activation. Furthermore, the somatostatin receptor SSTR2 antagonist CYN154806 could abolish somatostatin-induced NHE8 expression and p38 MAPK phosphorylation. Thus our data provided the first concrete evidence indicating that somatostatin stimulates intestinal Na(+) absorption by increasing intestinal NHE8 expression through the SSTR2-p38 MAPK pathway.
authors.affiliation: Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: Huacong
authors.initials: H
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Chengwei
authors.initials: C
authors.lastname: Tang
authors.forename: Fayez K
authors.initials: FK
authors.lastname: Ghishan
mesh_terms: D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology*; D018938:Caco-2 Cells; D002460:Cell Line; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008871:Microvilli / Q000378:metabolism; D015282:Octreotide / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000032:analysis / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis / Q000378:metabolism*
chemical_list: D000930:Antidiarrheals; C403089:CYN 154806; D009842:Oligopeptides; D017481:Receptors, Somatostatin; C486775:SLC9A8 protein, human; C471945:Slc9a8 protein, mouse; D017923:Sodium-Hydrogen Exchangers; D013004:Somatostatin; D012964:Sodium; C093733:somatostatin receptor 2; D048051:p38 Mitogen-Activated Protein Kinases; D015282:Octreotide