title: Chronic ethanol exposure impairs neuronal nitric oxide synthase in the rat intestine.
abstract: BACKGROUND
  Nitric oxide (NO), synthesized by neuronal (nNOS), endothelial (eNOS), and inducible (iNOS) nitric oxide synthases, plays an essential role in the physiological functions of the gastrointestinal (GI) tract. Chronic ethanol intake has been shown to interfere with several of these physiological functions, leading to the pathological alterations observed in alcoholic individuals. Our aim therefore was to investigate the effects of chronic ethanol consumption on NOS isoforms in different GI segments.
  
  
  METHODS
  Rats received either 20% aqueous ethanol solution or water for 8 weeks. Tissue samples of the duodenum, jejunum, ileum, and colon of the rats were used for measurement of the NOS activity, protein content, and nNOS immunohistochemistry. Anti-HuC/D immunohistochemistry was used to determine the total number of neurons.
  
  
  RESULTS
  Measurement of the physiological constitutive NOS (cNOS) activity revealed a 20 times higher activity in the colon than in the small intestine and after chronic ethanol treatment demonstrated a significant decrease in the jejunum, ileum, and colon, while in the duodenum it remained unchanged compared with the control group. The physiological iNOS activity was higher in the ileum and colon than in the duodenum and jejunum, and these levels were not significantly affected by ethanol. Neuronal nitric oxide synthase immunohistochemistry revealed a significant decrease in the numbers of immunostained cells in all investigated intestinal segments, while the total number of myenteric neurons remained constant. The nNOS protein content measured by Western blotting indicated a significant decrease in the colon after ethanol consumption, while in other intestinal segments change was not detectable.
  
  
  CONCLUSIONS
  This study has demonstrated for the first time that chronic ethanol consumption has a differential effect on NOS activity, NOS protein content, and the number of nitrergic neurons in different intestinal segments, suggesting that chronic ethanol administration affects the NO pathways in the enteric nervous system.
authors.affiliation: Department of Zoology and Cell Biology, University of Szeged, Szeged, Hungary. krecs@bio.u-szeged.hu
authors.forename: Monika
authors.initials: M
authors.lastname: Krecsmarik
authors.forename: Ferenc
authors.initials: F
authors.lastname: Izbéki
authors.forename: Mária
authors.initials: M
authors.lastname: Bagyánszki
authors.forename: Nikolett
authors.initials: N
authors.lastname: Linke
authors.forename: Nikolett
authors.initials: N
authors.lastname: Bódi
authors.forename: József
authors.initials: J
authors.lastname: Kaszaki
authors.forename: Zója
authors.initials: Z
authors.lastname: Katarova
authors.forename: Aron
authors.initials: A
authors.lastname: Szabó
authors.forename: Eva
authors.initials: E
authors.lastname: Fekete
authors.forename: Tibor
authors.initials: T
authors.lastname: Wittmann
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003106:Colon / Q000201:enzymology; D000431:Ethanol / Q000008:administration & dosage*; D007082:Ileum / Q000201:enzymology; D007150:Immunohistochemistry; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology* / Q000294:innervation; D007583:Jejunum / Q000201:enzymology; D008297:Male; D009197:Myenteric Plexus / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D052248:Nitric Oxide Synthase Type I / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000431:Ethanol; D052248:Nitric Oxide Synthase Type I