The beta3-adrenoceptor agonist SR58611A ameliorates experimental colitis in rats.
Neurogastroenterol Motil
; 20(9): 1030-41, 2008 Sep.
Article
in En
| MEDLINE
| ID: mdl-18492028
ABSTRACT
Beta(3)-adrenoceptor agonists protect against experimental gastric ulcers. We investigated the effects of the beta(3)-adrenoceptor agonist SR58611A on 2,4-dinitrobenzene sulphonic acid-induced colitis in rats and analysed the expression of beta(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-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels. Reverse transcription-polymerase chain reaction and immunohistochemical analysis were used to examine the expression of beta(3)-adrenoceptors. SR58611A significantly reduced the severity of colitis as well as the tissue levels of TNF-alpha, IL-1beta and IL-6. Colitis was associated with a decreased expression of beta(3)-adrenoceptor mRNA in the mucosal/submucosal layer of distal colon and this reduction was not affected by SR58611A. Immunohistochemical analysis revealed beta(3)-adrenoceptors within the muscularis externa, in myenteric neurons and nerve fibres and in the submucosa. beta(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 beta(3)-adrenoceptor agonist SR58611A suggests that beta(3)-adrenoceptors may represent a therapeutic target in gut inflammation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tetrahydronaphthalenes
/
Colitis
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Adrenergic beta-Agonists
/
Adrenergic beta-3 Receptor Agonists
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
Neurogastroenterol Motil
Journal subject:
GASTROENTEROLOGIA
/
NEUROLOGIA
Year:
2008
Document type:
Article
Affiliation country: