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Role of α9* nicotinic acetylcholine receptor in Murine Dextran Sodium Sulfate‐Induced Colitis Model
Author(s) -
AlSharari Shakir,
Toma Wisam,
McIntosh Michael,
Imad Damaj
Publication year - 2018
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.2018.32.1_supplement.840.6
Subject(s) - colitis , ulcerative colitis , nicotinic agonist , medicine , pharmacology , nicotine , nicotinic acetylcholine receptor , cholinergic , acetylcholine , muscarinic acetylcholine receptor , endocrinology , receptor , disease
Ulcerative colitis (UC) is largely a disease of nonsmokers and ex‐smokers and tobacco smoking affects on the disease course and severity. It has been suggested that smoking may protect against ulcerative colitis. Nicotine seems to be a key mediator of this response. Nicotinic acetylcholine receptors can regulate inflammation primarily through the vagus nerve via cholinergic anti‐inflammatory pathway. α9α10 nAChRs are new promising target of the neuronal nicotinic acetylcholine receptor, especially after the discovery of a novel selective α9α10 conotoxin antagonist. Administration of α9α10 selective α‐conotoxin antagonists have antinociception effect in neuropathic and tonic inflammatory pain animal models. However, little is known about the role of α9α10 nAChRs in experimental colitis. To our knowledge, we reported the first observation of the role of α9α10 nAChRs in the experimental animal colitis model. Methods C57BL6 Male adult mice were given DSS solution freely in the drinking water for 7 consecutive days after which tap water was given on the 8 th day. We measured a Disease Activity Index (DAI) that includes body weight loss, blood presence in stools, stool consistency, local rectal irritation and length of the colon. The mice were then sacrificed on day 8 to allow examination of the entire colon. Disease severity and colon tissue histology and tumor necrosis factor‐α (TNFα) were evaluated. TNF α was determined by enzyme‐linked immunosorbent assay analysis of colon samples. The present study seeks to determine the effect of α‐conotoxin RgIA (α‐RgIA) in DSS‐induced colitis model in adult male C57Bl/6 mice. Low doses of α‐conotoxin RgIA (α‐RgIA) treatment in DSS‐treated mice displayed a significantly decreased in DAI value as well as colonic level of TNF‐α (p<0.05) compared to the control group but high dose of α‐RgIA showed significant decrease in total histological damage scores. The highest dose partially reverse the shortening of the colon. The availability of α9* selective conotoxins against other nAChR subtypes has opened new avenues in pharmacology research and potential targets in the inflammatory disorders. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .