The beta3-adrenoceptor agonist SR58611A ameliorates experimental colitis in rats.
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.
Vasina
V
V
Department of Pharmacology, University of Bologna, Bologna, Italy.
Abu-Gharbieh
E
E
Barbara
G
G
de Giorgio
R
R
Colucci
R
R
Blandizzi
C
C
Bernardini
N
N
Croci
T
T
Del Tacca
M
M
de Ponti
F
F
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000818:Animals; D001835:Body Weight; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D016207:Cytokines; D022702:Receptors, Adrenergic, beta-3; D013764:Tetrahydronaphthalenes; C045305:2,4-dinitrofluorobenzene sulfonic acid; D004139:Dinitrofluorobenzene; D019009:Proto-Oncogene Proteins c-kit; C076252:amibegron