Somatostatin stimulates intestinal NHE8 expression via p38 MAPK pathway

Chunhui Wang, Hua Xu, Huacong Chen, Jing Li, Bo Zhang, Chengwei Tang, Fayez K. Ghishan

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)C375-C382
JournalAmerican Journal of Physiology - Cell Physiology
Volume300
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • D-cells
  • Diarrhea
  • Sodium/hydrogen exchanger

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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