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.
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Authors | V Vasina, E Abu-Gharbieh, G Barbara, R de Giorgio, R Colucci, C Blandizzi, N Bernardini, T Croci, M Del Tacca, F de Ponti |
Journal | Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
(Neurogastroenterol Motil)
Vol. 20
Issue 9
Pg. 1030-41
(Sep 2008)
ISSN: 1365-2982 [Electronic] England |
PMID | 18492028
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adrenergic beta-3 Receptor Agonists
- Adrenergic beta-Agonists
- Cytokines
- Receptors, Adrenergic, beta-3
- Tetrahydronaphthalenes
- 2,4-dinitrofluorobenzene sulfonic acid
- Dinitrofluorobenzene
- Proto-Oncogene Proteins c-kit
- amibegron
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Topics |
- Adrenergic beta-3 Receptor Agonists
- Adrenergic beta-Agonists
(therapeutic use)
- Animals
- Body Weight
- Colitis
(chemically induced, drug therapy, pathology)
- Colon
(cytology, metabolism, pathology)
- Cytokines
(immunology)
- Dinitrofluorobenzene
(analogs & derivatives, pharmacology)
- Dose-Response Relationship, Drug
- Humans
- Inflammation
(chemically induced, metabolism, pathology)
- Male
- Proto-Oncogene Proteins c-kit
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Receptors, Adrenergic, beta-3
(genetics, metabolism)
- Tetrahydronaphthalenes
(therapeutic use)
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