Iron deficiency diminishes gallbladder neuronal nitric oxide synthase.
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.
Swartz-Basile
D A
DA
Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Goldblatt
M I
MI
Blaser
C
C
Decker
P A
PA
Ahrendt
S A
SA
Sarna
S K
SK
Pitt
H A
HA
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
D014168:Transferrin; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D012844:Sincalide