Expression and role of 5-HT7 receptor in brain and intestine in rats with irritable bowel syndrome

• Published in: Chinese medical journal 2007-12, Vol.120 (23), p.2069-2074
• Main Authors: Zou, Bai-cang, Dong, Lei, Wang, Yan, Wang, Sheng-hao, Cao, Ming-bo
• Format: Article
• Language: English
• Subjects: 5-羟色胺; 5-羟色胺7受体; Animals; Brain - metabolism; Cyclic AMP - metabolism; Disease Models, Animal; Immunohistochemistry; Intestines - metabolism; Irritable Bowel Syndrome - etiology; Irritable Bowel Syndrome - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Serotonin - analysis; Receptors, Serotonin - genetics; Receptors, Serotonin - physiology; Serotonin - analysis; 易激性肠综合征; 环腺苷酸
• ISSN: 0366-6999; 2542-5641
• DOI: 10.1097/00029330-200712010-00002

Background The 5-hydroxytryptamine7 receptor （5-HT7 receptor, 5-HTTR） plays an important role in the regulation of smooth muscle relaxation and visceral sensation and might be involved in the pathogenesis of the gastrointestinal dyskinesia, abdominal pain and visceral paresthesia in irritable bowel syndrome （IBS）. The aim of this study was to investigate the role of the 5-HT7 receptor in the pathogenesis of IBS. Methods A rat model of irritable bowel syndrome with diarrhea （IBS-D） was established by colonic instillation of acetic acid and restraint stress. A rat model with irritable bowel syndrome with constipation （IBS-C） was established by stomach irrigated with 0-4℃ cool water daily for 14 days. The content and distribution of 5-HT in the brain and gut were examined by immunohistochemistry and the mRNA expression of the 5-HT7 receptor was determined by fluorescent quantitative reverse transcription polymerase chain reaction. The accumulation of cyclic adenosine monophosphate （cAMP） in all the same tissues was measured by radioimmunity. Results The models of IBS were reliable by identification. The immunohistochemistry results showed that there were significantly more 5-HT positive cells in the IBS-D group than in the control group in the hippocampus, hypothalamus, jejunum, ileum, proximate colon and distal colon （P〈0.05）, as well as more than were found in the IBS-C group in jejunum and ileum （P〈0.05）. There were more 5-HT positive cells in the IBS-C group than in the control hippocampus, hypothalamus, ileum, proximate colon, and distal colon （P〈0.05）. Real time-PCR results showed that the expression level of the 5-HT7 receptor in both the IBS-C and IBS-D groups were enhanced compared with the control group in the hippocampus and hypothalamus （P〈0.05）. The expression level of 5-HT7 receptors in the IBS-C group was notably greater when compared with the controls in the ileum and colon （P〈0.05）. The cAMP accumulation in the hippocampus and hypothalamus in both the IBS-C and IBS-D groups was higher than that in the control group （P〈0.01 and P〈0.05）. The cAMP accumulation in the tBS-C group was higher than that in the control group in the proximal and distal colon （m〈o.o5）. Conclusions The increased 5-HT content in the brain and intestine is related to the IBS pathogenesis. The up-regulated expression of the 5-HT7 receptor in the brain and colon might play an important role in the pathogenesis of IBS-C.