ISSN:
1573-2568
Keywords:
second messengers
;
calcium
;
trifluoperazine
;
ionophore
;
ion flux
;
electrophysiology
;
Ussing chamber
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Gallbladder absorption is increased prior to gallstone formation in prairie dogs and may promote cholesterol crystallization. Recent studies indicate that Ca2+-calmodulin (CaM) tonically inhibits gallbladder electrolyte absorption in prairie dogs fed a nonlithogenic diet. We hypothesized that dietary cholesterol alters CaM-dependent regulation of gallbladder ion transport, a possible link between increased gallbladder absorption and gallstone formation. Gallbladders from prairie dogs fed control (N = 24) or 1.2% cholesterol-enriched chow (N = 32) were mounted in Ussing chambers. Electrophysiology and ion flux were measured while exposing the epithelia sequentially to trifluoperazine (TFP), a CaM antagonist, followed by the calcium ionophore A23187. Animals fed the high cholesterol diet developed crystals and gallstones in a time-dependent fashion. Mucosal addition of 50 μM TFP decreased short-circuit current (Isc), transepithelial potential, and tissue conductance in control, crystal, and gallstone animals, but the magnitude of its effect was significantly decreased in animals fed cholesterol. TFP stimulated mucosa-to-serosa Na+ flux by 6.9 ± 0.9 μeq/cm2/hr in control animals but only 3.1 ± 0.8 μeq/cm2/hr in gallstone animals. Similarly, TFP increased mucosa-to-serosa Cl− flux by 11.9 ± 1.4 μeq/cm2/hr in controls but only 4.9 ± 1.4 μeq/cm2/hr in cholesterol-fed animals. TFP effects were not reversed by A23187, which caused differential effects on Isc and ion transport in cholesterol-fed animals. In conclusion, CaM-mediated inhibition of gallbladder Na+ and Cl− transport is diminished in prairie dogs fed cholesterol. We conclude that gallbladder ion transport is partially released from basal inhibition during gallstone formation and propose that dysfunctional CaM regulation may be a stimulus to increased gallbladder absorption.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1005576608481
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