title: Chronic alcohol consumption induces an overproduction of NO by nNOS- and iNOS-expressing myenteric neurons in the murine small intestine.
abstract: BACKGROUND
  There are indications that alterations in the nitric oxide (NO) system of relaxation mediate gastrointestinal motor disturbances induced by chronic alcohol consumption (CAC). As CAC is known to inhibit the motility of the mouse small intestine, we investigated in this model if CAC affects basal NO synthesis by myenteric neurons and which NOS isoforms are involved.
  
  
  METHODS
  The instantaneous NO synthesis of individual neurons was optically measured in whole-mount preparations loaded with the NO synthesis indicator DAF-FM, and the expression of nNOS, iNOS and eNOS was determined by immunohistochemistry.
  
  
  RESULTS
  The DAF-FM recordings showed that CAC induced an increase in neuronal NO synthesis (absolute fluorescence: control 34±12; CAC 140±56; mean±SD; P<0.0004). Neurons of control mice expressed the nNOS (29±3% of total) and iNOS (28±1%) isoforms. eNOS expression was observed in <0.5% of the neurons. Chronic alcohol consumption caused an increase in the proportion of iNOS-expressing neurons (to 33±5%; P<0.01) and a decrease in nNOS-expressing neurons (to 22±3%; P<0.0001), without altering the proportion of NO-producing neurons (control 55±13%; CAC 56± 11%; P=0.82).
  
  
  CONCLUSIONS
  Chronic alcohol consumption induces a marked increase in NO synthesis by jejunal myenteric neurons, accompanied by an up-regulation of iNOS-expressing neurons and a downregulation of nNOS neurons. We conclude that the overproduction of NO may be a direct cause of gastrointestinal motility disturbances.
authors.affiliation: Laboratory of Cell Biology & Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Bagyánszki
authors.forename: P
authors.initials: P
authors.lastname: Torfs
authors.forename: M
authors.initials: M
authors.lastname: Krecsmarik
authors.forename: E
authors.initials: E
authors.lastname: Fekete
authors.forename: D
authors.initials: D
authors.lastname: Adriaensen
authors.forename: L
authors.initials: L
authors.lastname: Van Nassauw
authors.forename: J-P
authors.initials: JP
authors.lastname: Timmermans
authors.forename: A B A
authors.initials: AB
authors.lastname: Kroese
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D007421:Intestine, Small / Q000294:innervation* / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009197:Myenteric Plexus / Q000166:cytology*; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse