Somatostatin stimulates intestinal NHE8 expression via p38 MAPK pathway

Am J Physiol Cell Physiol. 2011 Feb;300(2):C375-82. doi: 10.1152/ajpcell.00421.2010. Epub 2010 Nov 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidiarrheals / pharmacology*
  • Caco-2 Cells
  • Cell Line
  • Female
  • Humans
  • Intestinal Absorption / drug effects
  • Intestine, Small / drug effects*
  • Intestine, Small / metabolism
  • Mice
  • Microvilli / metabolism
  • Octreotide / pharmacology*
  • Oligopeptides / pharmacology
  • Phosphorylation / drug effects
  • Receptors, Somatostatin / antagonists & inhibitors
  • Sodium / metabolism
  • Sodium-Hydrogen Exchangers / analysis
  • Sodium-Hydrogen Exchangers / metabolism*
  • Somatostatin / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / analysis
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Antidiarrheals
  • CYN 154806
  • Oligopeptides
  • Receptors, Somatostatin
  • SLC9A8 protein, human
  • Slc9a8 protein, mouse
  • Sodium-Hydrogen Exchangers
  • Somatostatin
  • Sodium
  • somatostatin receptor 2
  • p38 Mitogen-Activated Protein Kinases
  • Octreotide