title: Increased expression of 5-HT3 and NK 1 receptors in 5-fluorouracil-induced mucositis in mouse jejunum.
abstract: 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.
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo, Togane, Chiba, 283-8555, Japan, kenjiro@jiu.ac.jp.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Nakajima
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.forename: Sae
authors.initials: S
authors.lastname: Kato
authors.forename: Atsunobu
authors.initials: A
authors.lastname: Sagara
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Arakawa
authors.forename: Kimihito
authors.initials: K
authors.lastname: Tashima
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Syunji
authors.initials: S
authors.lastname: Horie
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000009:adverse effects*; D007579:Jejunal Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D052016:Mucositis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D019899:Paracrine Communication; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis* / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000096:biosynthesis* / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018040:Receptors, Neurokinin-1; D044406:Receptors, Serotonin, 5-HT3; D013373:Substance P; D005472:Fluorouracil