Increased Expression of 5-HT3 and NK1 Receptors in 5-Fluorouracil-Induced Mucositis in Mouse Jejunum

详细信息    查看全文

• 作者：Kenjiro Matsumoto (1) (2)
  Tomoharu Nakajima (1)
  Hiroyasu Sakai (2)
  Sae Kato (1)
  Atsunobu Sagara (2)
  Kazuhiko Arakawa (2)
  Kimihito Tashima (1)
  Minoru Narita (2)
  Syunji Horie (1)
  
• 关键词：5 ; Fluorouracil ; 5 ; HT3 receptors ; NK1 receptors ; Immunohistochemistry ; Jejunum
• 刊名：Digestive Diseases and Sciences
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：58
• 期：12
• 页码：3440-3451
• 全文大小：
• 作者单位：Kenjiro Matsumoto (1) (2)
  Tomoharu Nakajima (1)
  Hiroyasu Sakai (2)
  Sae Kato (1)
  Atsunobu Sagara (2)
  Kazuhiko Arakawa (2)
  Kimihito Tashima (1)
  Minoru Narita (2)
  Syunji Horie (1)
  
  1. Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo, Togane, Chiba, 283-8555, Japan
  2. Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan
  
• ISSN：1573-2568

文摘

Background and Objective Although 5-fluorouracil (5-FU) is a widely used as chemotherapy agent, severe mucositis develops in approximately 80?% of patients. 5-FU-induced small intestinal mucositis can cause nausea and vomiting. The current study was designed to investigate peripheral alterations due to the 5-FU-induced mucositis of neuronal and non-neuronal 5-HT3 and NK1 receptor expression by immunohistochemical analysis. Methods 5-FU was administered by i.p. injection to C57BL/6 mice. After 4?days, segments of the jejunum were removed. The specimens were analyzed by immunohistochemistry, real-time PCR, and enzyme immunoassay. Results The numbers of 5-HT3 receptor immunopositive cells and nerve fibers in mucosa were increased by 5-FU treatment. The 5-HT3 receptor immunopositive cell bodies were found only in jejunal submucosa and myenteric plexus in the 5-FU-treated mice. The numbers of NK1 receptor cells in mucosa and immunopositive expression of NK1 receptors in deep muscular plexus were dramatically increased in 5-FU-treated mice. Real-time PCR demonstrated that 5-FU treatment significantly increased mRNA levels of 5-HT3A, 5-HT3B, and NK1 receptors. The amounts of 5-HT and substance P increased after 5-FU treatment. The 5-HT3 or NK1 receptor immunopositive cells colocalized with both 5-HT and substance P. Furthermore, 5-HT3 and NK1 receptors colocalized with CD11b. Conclusions The 5-HT3 and NK1 immunopositive macrophages and mucosal mast cells in lamina propria release 5-HT and substance P, which in turn activate their corresponding receptors on mucosal cells in autocrine and paracrine manners. It is assumed to result in the release of 5-HT and substance P in mucosa.