Galanin-1 receptor up-regulation mediates the excess colonic fluid production caused by infection with enteric pathogens.
Galanin is widely distributed in enteric nerve terminals lining the gastrointestinal tract. We previously showed that pathogenic Escherichia coli, but not normal commensal organisms, increase galanin-1 receptor expression by epithelial cells lining the colon (i.e., colonocytes). When present, galanin-1 receptor activation by ligand causes colonocyte Cl- secretion. We herein demonstrate that disparate pathogens including Salmonella typhimurium and Shigella flexerii also increase colonocyte galanin-1 receptor expression, whose activation is responsible for a principal component of the increased colonic fluid secretion observed. Although eliminating the GAL1R gene by homologous recombination does not alter basal colonic fluid secretion, removal of one or both alleles completely attenuates the increase in fluid secretion due to infection with enteric pathogens. Galanin-1 receptor up-regulation therefore represents a novel mechanism accounting for the increased colonic fluid secretion observed in infectious diarrhea due to several different pathogens.
Matkowskyj
K A
KA
Department of Medicine, University of Illinois at Chicago and Chicago Veterans Administration Medical Center (West Side Division), Chicago, Illinois 60612, USA.
Danilkovich
A
A
Marrero
J
J
Savkovic
S D
SD
Hecht
G
G
Benya
R V
RV
D000818:Animals; D001826:Body Fluids / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D004755:Enterobacteriaceae / Q000472:pathogenicity*; D004756:Enterobacteriaceae Infections / Q000378:metabolism*; D007419:Intestinal Secretions / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide / Q000096:biosynthesis*; D012486:Salmonella typhimurium / Q000472:pathogenicity; D012763:Shigella flexneri / Q000472:pathogenicity; D015854:Up-Regulation
D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide