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Galanin-1 receptor up-regulation mediates the excess colonic fluid production caused by infection with enteric pathogens

Nature Medicine volume 6, pages 1048–1051 (2000)Cite this article

Abstract

Galanin is widely distributed in enteric nerve terminals lining the gastrointestinal tract1,2. We previously showed that pathogenic Escherichia coli, but not normal commensal organisms, increase galanin-1 receptor expression by epithelial cells lining the colon3 (i.e., colonocytes). When present, galanin-1 receptor activation by ligand causes colonocyte Cl− secretion 4. 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.

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Figure 1: Gal1-R expression and colonic fluid secretion in wild-type C57BL/6J mice after gavage with the indicated enteric pathogen.
Figure 2: Generation and consequence of eliminating the GAL1R gene from C57BL/6J mice.

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Acknowledgements

This work was supported by a Student Research Award of the American Digestive Health Foundation (to K.M.); by a Post Doctoral Fellowship Award of the Crohn's and Colitis Foundation of America (to S.S.), by National Institutes of Health (NIH) grant DK-50694, a VA Merit Review and a VA Research Enhancement Awards Program (REAP) (to G.H.); and by NIH grant DK-54777, a VA Merit Review and a VA-REAP (to R.V.B.).

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Authors and Affiliations

  1. Department of Medicine, University of Illinois at Chicago and Chicago Veterans Administration Medical Center (West Side Division), Chicago, 60612, Illinois

    Kristina A. Matkowskyj, Alexey Danilkovich, Jorge Marrero, Suzana D. Savkovic, Gail Hecht & Richard V. Benya

  2. Department of Pathology, University of Illinois at Chicago and Chicago Veterans Administration Medical Center (West Side Division), Chicago, 60612, Illinois

    Kristina A. Matkowskyj

  3. Department of Microbiology and Immunology, University of Illinois at Chicago and Chicago Veterans Administration Medical Center (West Side Division), Chicago, 60612, Illinois

    Gail Hecht

  4. Department of Pharmacology, University of Illinois at Chicago and Chicago Veterans Administration Medical Center (West Side Division), Chicago, 60612, Illinois

    Richard V. Benya

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  1. Kristina A. Matkowskyj
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  2. Alexey Danilkovich
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  4. Suzana D. Savkovic
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Correspondence to Richard V. Benya.

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Matkowskyj, K., Danilkovich, A., Marrero, J. et al. Galanin-1 receptor up-regulation mediates the excess colonic fluid production caused by infection with enteric pathogens. Nat Med 6, 1048–1051 (2000). https://doi.org/10.1038/79563

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