title: Iron deficiency diminishes gallbladder neuronal nitric oxide synthase.
abstract: BACKGROUND
  Iron deficiency has been demonstrated in the prairie dog to result in cholesterol crystal formation and altered biliary motility. Gallbladder filling and emptying are influenced by both inhibitory and excitatory stimuli, with nitric oxide (NO) playing a key role in normal relaxation. Iron is a cofactor for nitric oxide synthase. Therefore, we tested the hypothesis that iron deficiency would result in diminished levels of gallbladder neuronal nitric oxide synthase (nNOS) but would not influence the gallbladder's response to excitatory stimuli.
  
  
  METHODS
  Twenty adult female prairie dogs were fed either an iron-supplemented (Fe(+)) (200 ppm) control diet (n = 10) or an iron-deficient (Fe-) (8 ppm) diet (n = 10) for 8 weeks. Fasting gallbladder volume was measured. Gallbladder muscle strips were harvested for response to excitatory stimuli and measurement of nNOS protein levels by Western blotting. Muscle strip response to a spectrum of doses of cholecystokinin, acetylcholine, and electrical field stimuli was determined, and the areas under the response curves were calculated.
  
  
  RESULTS
  Gallbladder volume increased in the iron-deficient prairie dogs compared with the iron-supplemented group (1.45 +/- 0.27 mL vs 0.80 +/- 0.13 mL, P < 0.05). Iron deficiency diminished the ratio of gallbladder nNOS to beta-actin protein levels (0.05 +/- 0.01 vs 3.48 +/- 1.02, P < 0.05) but resulted in a normal response to excitatory stimuli.
  
  
  CONCLUSIONS
  We conclude that diminished gallbladder neuronal nitric oxide synthase contributes to the gallbladder stasis that occurs with iron deficiency. This phenomenon may contribute to the increased incidence of gallstones in premenopausal women.
authors.affiliation: Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Swartz-Basile
authors.forename: M I
authors.initials: MI
authors.lastname: Goldblatt
authors.forename: C
authors.initials: C
authors.lastname: Blaser
authors.forename: P A
authors.initials: PA
authors.lastname: Decker
authors.forename: S A
authors.initials: SA
authors.lastname: Ahrendt
authors.forename: S K
authors.initials: SK
authors.lastname: Sarna
authors.forename: H A
authors.initials: HA
authors.lastname: Pitt
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D002769:Cholelithiasis / Q000209:etiology / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004285:Dogs; D005260:Female; D005704:Gallbladder / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D000090463:Iron Deficiencies; D009119:Muscle Contraction / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D012844:Sincalide / Q000494:pharmacology; D014168:Transferrin / Q000378:metabolism
chemical_list: D014168:Transferrin; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D012844:Sincalide