Journal article
Calmodulin regulation of gallbladder ion transport becomes dysfunctional during gallstone formation in prairie dogs
Digestive diseases and sciences, v 45(7), pp 1422-1430
01 Jul 2000
PMID: 10961724
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 microM 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 microeq/cm2/hr in control animals but only 3.1 +/- 0.8 microeq/cm2/hr in gallstone animals. Similarly, TFP increased mucosa-to-serosa Cl- flux by 11.9 +/- 1.4 microeq/cm2/hr in controls but only 4.9 +/- 1.4 microeq/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.
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Details
- Title
- Calmodulin regulation of gallbladder ion transport becomes dysfunctional during gallstone formation in prairie dogs
- Creators
- A Moser - Philadelphia VA Medical CenterDan GiurgiuKenneth Morgenstern - Hahnemann University HospitalZahidur Abedin - Hahnemann University HospitalMohammad Z Abedin
- Publication Details
- Digestive diseases and sciences, v 45(7), pp 1422-1430
- Publisher
- Springer Nature B.V
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000088852500025
- Scopus ID
- 2-s2.0-0033898883
- Other Identifier
- 991019319083004721
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- Web of Science research areas
- Gastroenterology & Hepatology