title: Pannexin-2 is expressed in the human colon with extensive localization in the enteric nervous system.
abstract: BACKGROUND
  Pannexin-2 (Panx2) is a member of the novel group of membrane spanning protein channels present in the central nervous system. Limited studies have examined Panx2 in the intestine, where it may have important physiological roles. The present study characterized Panx2 expression and localization in the human colon in health and disease states.
  
  
  METHODS
  Immunofluorescence determined Panx2 localization and co-localization, and quantitative real-time PCR and Western blot determined gene and protein expression in ulcerative colitis (UC), Crohn's disease (CD), and control human colon.
  
  
  RESULTS
  Panx2 was widely expressed in myenteric and submucosal ganglia, particularly in the cytoplasm of neurons. Panx2 was also expressed on smooth muscle of the muscularis and blood vessels, some non-lymphoid leukocytes, mast cells, and mucosal epithelial cells. Co-localization of Panx2 occurred with β-tubulin, neuronal nitric oxide synthase, substance P, vesicular acetylcholine transporter, and calcitonin gene-related peptide, indicating widespread Panx2 expression in extrinsic and intrinsic neurons. Molecular studies revealed a 3.4-fold higher level of Panx2 mRNA in ascending compared to sigmoid muscularis (p < 0.05), despite similar protein levels. Similarly, UC muscularis showed a 35-fold up-regulation in Panx2 mRNA, but not in protein (p < 0.05).
  
  
  CONCLUSIONS
  Here, we demonstrated the dense expression of Panx2 in the enteric nervous system and the co-localization of Panx2 with a spectrum of neuronal markers, indicating that Panx2 may be involved in mediating neurotransmission in the colon. The substantial increase in Panx2 mRNA in UC muscle but not protein suggests that the Panx2 translation process may be disrupted in UC.
authors.affiliation: School of Medical Sciences, UNSW Australia, Sydney, NSW, Australia.
authors.forename: E F
authors.initials: EF
authors.lastname: Diezmos
authors.forename: S L
authors.initials: SL
authors.lastname: Sandow
authors.forename: D S
authors.initials: DS
authors.lastname: Perera
authors.forename: D W
authors.initials: DW
authors.lastname: King
authors.forename: P P
authors.initials: PP
authors.lastname: Bertrand
authors.forename: L
authors.initials: L
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D044682:Colon, Ascending / Q000378:metabolism; D012809:Colon, Sigmoid / Q000378:metabolism; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism; D017615:Enteric Nervous System / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013373:Substance P / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D017630:Connexins; C492765:PANX2 protein, human; D012333:RNA, Messenger; D050494:Vesicular Acetylcholine Transport Proteins; D013373:Substance P; D052248:Nitric Oxide Synthase Type I; D015740:Calcitonin Gene-Related Peptide
keywords: enteric nervous system; human colon; pannexin-2; ulcerative colitis