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Neuropeptide Y mediated increase in neuronal nitric oxide synthase (nNOS) leads to colitis and impaired colonic motility
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1183.4
Subject(s) - colitis , neuropeptide y receptor , nitric oxide synthase , chemistry , inflammation , myeloperoxidase , endocrinology , medicine , motility , oxidative stress , nitric oxide , glutathione , biochemistry , neuropeptide , biology , enzyme , receptor , genetics
The role of NPY from enteric neurons in inflammation has not been studied. We examined the role of neuronal NPY and nitric oxide synthase (nNOS) in modulating colitis. Colitis was induced with Dextran Sodium Sulfate (DSS)/streptomycin pre‐treated Salmonella typhimurium (S.T.) in wild type (WT) and nNOS (nNOS −/− ) knock out mice. In WT mice, DSS/S.T. induced an increase in enteric neuronal NPY and nNOS expression. WT mice were more susceptible to inflammation compared to nNOS −/− (higher histological scores (10 ± 0.5), and myeloperoxidase (MPO) activity (0.23 ± 0.9, n = 4, p<0.01)). DSS‐WT mice had increased nitrite and nitro tyrosine, decreased glutathione (GSH) levels and increased catalase activity. The inflammation also resulted in chronic impairment of colonic motility in DSS‐treated WT mice. The lower histological scores, MPO and KC were observed in nNOS −/− and NPY −/− /nNOS −/− mice (n= 4, p < 0.001). We propose that NPY‐mediated increase in nNOS is a determinant of oxidative stress and subsequent inflammation.