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Exendin-4,an analogue of Glucagon-like peptide-1,attenuates hyperalgesia through serotonergic pathways in rats with neonatal colonic sensitivity
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نویسنده
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yang y. ,cui x. ,chen y. ,wang y. ,li x. ,lin l. ,zhang h.
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منبع
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journal of physiology and pharmacology - 2014 - دوره : 65 - شماره : 3 - صفحه:349 -357
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چکیده
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Glucagon-like peptide-1 (glp-1) analogue rose-010 can provide effective pain relief from irritable bowel syndrome (ibs). however,the underlying biological mechanism is still unknown. here,we investigate the effect of glp-1 analogue exendin-4 on visceral hypersensitivity in colonic sensitized rats. rat models of visceral hypersensitivity were established by intra-colonic infusion of acetic acid in 10-day-old sprague-dawley rats. visceral sensitivity was assessed by measurement of abdominal withdrawal reflex (awr) and electromyography (emg). exendin-4 with doses of 1,5,and 10 ∞g/kg were intraperitoneally administered,respectively. the expressions of serotonin transporter (sert) and tryptophan hydroxylase-1 (tph-1) in colonic tissues were detected by rt-pcr and western blot,respectively. the levels of serotonin (5-ht) and glp-1 were measured by elisa assay. visceral hypersensitivity after neonatal colonic sensitization was verified. the colonic sensitized rats showed low levels of glp-1 in plasma and high levels of 5-ht in plasma and colonic tissue (p<0.05). exendin-4 dose-dependently reduced visceral hypersensitivity in colonic sensitized rats. the awr scores in colonic sensitized rats with exendin-4 (5 ∞g/kg) reduced to 1.56±0.53 (p=0.013 vs. 2.33±0.50),2.23±0.45 (p=0.008 vs. 3.0±0.5) during crd at 40,and 60 mmhg,respectively. similar findings were showed at dose of 10 ∞g/kg. exendin-4 (5 ∞g/kg and 10 ∞g/kg) reduced the emg during crd at 40,60,80 mmhg (p<0.01). exendin-4 (5.0 ∞g/kg or 10.0 ∞g/kg) significantly decreased the 5-ht colonic levels (2.343±0.447,2.175±0.360 ng/100 mg vs. 3.607±0.628 ng/100 mg,p<0.05). the sert protein expressions in colonic tissues in colonic sensitized rats were significantly increased with exendin-4 at doses of 1,5 or 10 ug/kg (0.759±0.068,0.942±0.037,0.944±0.097 vs. 0.552±0.047,p<0.05,respectively),and the sert mrna expression also increased after treatment with exendin-4. the colonic sensitized rats showed lower tph-1 levels after treatment with exendin-4 (p<0.05). these findings suggest that exendin-4 reduce visceral hypersensitivity and this may be associated with up-regulating sert expression,and down-regulating tph-1 expression.
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کلیدواژه
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Glucagon-like peptide-1; Irritable bowel syndrome; Serotonin transporter; Tryptophan hydroxylase-1; Visceral hypersensitivity
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آدرس
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department of gastroenterology,the first affiliated hospital of nanjing medical university,nanjing, China, department of gastroenterology,the first affiliated hospital of nanjing medical university,nanjing, China, department of gastroenterology,the affiliated hospital of taishan medical university,taian, China, department of gastroenterology,the first affiliated hospital of nanjing medical university,nanjing, China, department of gastroenterology,the first affiliated hospital of nanjing medical university,nanjing, China, department of gastroenterology,the first affiliated hospital of nanjing medical university,nanjing, China, department of gastroenterology,the first affiliated hospital of nanjing medical university,nanjing, China
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Authors
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