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The β 3 ‐adrenoceptor agonist SR58611A ameliorates experimental colitis in rats
Author(s) -
Vasina V.,
Abugharbieh E.,
Barbara G.,
De Giorgio R.,
Colucci R.,
Blandizzi C.,
Bernardini N.,
Croci T.,
Del Tacca M.,
De Ponti F.
Publication year - 2008
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2008.01138.x
Subject(s) - colitis , myenteric plexus , agonist , submucosa , immunohistochemistry , medicine , tumor necrosis factor alpha , endocrinology , receptor , inflammation , myeloperoxidase
Abstract β 3 ‐Adrenoceptor agonists protect against experimental gastric ulcers. We investigated the effects of the β 3 ‐adrenoceptor agonist SR58611A on 2,4‐dinitrobenzene sulphonic acid‐induced colitis in rats and analysed the expression of β 3 ‐adrenoceptors in the colonic wall. SR58611A was administered orally (1–10 mg kg −1 ) for 7 days, starting the day before induction of colitis. Colitis was assessed by macroscopic and histological scores, tissue myeloperoxidase activity, interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α) levels. Reverse transcription‐polymerase chain reaction and immunohistochemical analysis were used to examine the expression of β 3 ‐adrenoceptors. SR58611A significantly reduced the severity of colitis as well as the tissue levels of TNF‐α, IL‐1β and IL‐6. Colitis was associated with a decreased expression of β 3 ‐adrenoceptor mRNA in the mucosal/submucosal layer of distal colon and this reduction was not affected by SR58611A. Immunohistochemical analysis revealed β 3 ‐adrenoceptors within the muscularis externa, in myenteric neurons and nerve fibres and in the submucosa. β 3 ‐Adrenoceptor immunoreactivity was decreased in inflamed tissues compared to controls, particularly in the myenteric plexus; this reduction was counteracted by SR58611A. Amelioration of experimental colitis by the selective β 3 ‐adrenoceptor agonist SR58611A suggests that β 3 ‐adrenoceptors may represent a therapeutic target in gut inflammation.