Dextran sulfate sodium-induced murine colitis activates NF-κB and increases galanin-1 receptor expression

Jorge A. Marrero, Kristina A. Matkowskyj, Kenny Yung, Gail Hecht, Richard V. Benya

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Galanin is widely distributed in enteric nerve terminals and acts to modulate intestinal motility by altering smooth muscle contraction. This ligand causes Cl- secretion when colonic epithelial cells express the galanin-1 receptor (Gal1-R) subtype. Because Gal1-R expression by colonic epithelia is upregulated by the transcription factor nuclear factor-κB (NF- κB), increasingly appreciated as critical in the pathophysiology of inflammatory bowel disease, we wondered whether the diarrhea associated with this condition could be due to NF-κB-mediated increases in Gal1-R expression. To test this hypothesis, we provided oral dextran sulfate sodium (DSS) to C57BL/6J mice. Although Gal1-R are not normally expressed by epithelial cells lining the mouse colon, DSS treatment resulted in increased NF-κB activation and Gal1-R expression. Whereas galanin had no effect on murine colonic tissues studied ex vivo, it progressively increased short- circuit current and colonic fluid secretion in DSS-treated mice. Concomitant parenteral administration of the NF-κB inhibitor dexamethasone attenuated the activation of this transcription factor by DSS, inhibiting the increase in Gal1-R expression. Although Gal1-R-specific antagonists do not exist, intracolonic administration of commercially available galanin antibody diminished the DSS-induced increase in colonic fluid accumulation. Overall, these data demonstrate that a significant component of the excessive fluid secretion observed in DSS-treated mice is due to increased Gal1-R expression.

Original languageEnglish (US)
Pages (from-to)G797-G804
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume278
Issue number5 41-5
DOIs
StatePublished - May 2000

Keywords

  • Galanin
  • Inflammatory bowel disease
  • Secretion

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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