Iron deficiency diminishes gallbladder neuronal nitric oxide synthase. J Surg Res 2000 May 01;90(1):26-31
Date
04/27/2000Pubmed ID
10781371DOI
10.1006/jsre.2000.5827Scopus ID
2-s2.0-0034193631 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
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.
MATERIALS AND 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.
Author List
Swartz-Basile DA, Goldblatt MI, Blaser C, Decker PA, Ahrendt SA, Sarna SK, Pitt HAAuthor
Matthew I. Goldblatt MD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlotting, Western
Body Weight
Cholelithiasis
Cholesterol
Dogs
Female
Gallbladder
Muscle Contraction
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Sincalide
Transferrin