Galanin contributes to the excess colonic fluid secretion observed in dextran sulfate sodium murine colitis.
Galanin is present in enteric nerves lining the gastrointestinal (GI) tract where it is normally involved in regulating intestinal motility by binding to the galanin-1 receptor (Gal1R) subtype expressed by smooth muscle cells. In contrast, although epithelial cells lining the colon do not normally express Gal1R, this protein is up-regulated by the inflammation-associated transcription factor NF-kappaB. We previously showed that the murine colitis induced by dextran sulfate sodium (DSS) was associated with increased Gal1R expression as well as by increased colonic fluid secretion. Although Gal1R up-regulation by colonic epithelial cells results in increased intestinal Cl- secretion, the relative contributions of galanin to this excess colonic fluid secretion could not be determined. We therefore created a mouse genetically incapable of synthesizing Gal1R (GAL1R-/- mice). We herein demonstrate that both wild-type and GAL1R-/- mice developed identical histologic lesions in response to DSS. This was characterized by a marked inflammatory infiltrate, activation of NF-kappaB in both enterocytes and enteric nerves, and a threefold increase in neuronal galanin. Colonic fluid secretion, while increased, was approximately half that in GAL1R-/- mice as compared with their wild-type littermates. Overall, then, these findings strongly suggest that approximately half of the increase in colonic fluid secretion in DSS colitis is due to up-regulation of the Gal1R.
Matkowskyj
Kristina A
KA
Departments of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Nathaniel
Rajkumar
R
Prasad
Roli
R
Weihrauch
Dirk
D
Rao
Mrinalini
M
Benya
Richard V
RV
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage; D003092:Colitis / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D016264:Dextran Sulfate / Q000008:administration & dosage; D003967:Diarrhea / Q000503:physiopathology*; D004195:Disease Models, Animal; D019004:Galanin / Q000494:pharmacology*; D005838:Genotype; D007150:Immunohistochemistry; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D044091:Receptor, Galanin, Type 1 / Q000235:genetics / Q000502:physiology*; D014882:Water-Electrolyte Balance
D000925:Anticoagulants; D044091:Receptor, Galanin, Type 1; D019004:Galanin; D016264:Dextran Sulfate