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Updated: Sep 30, 2026

Gastrointestinal Motility Monitor (GIMM)
Published on: December 1, 2010
The effect of phosphodiesterase inhibition on gallbladder motility in vitro
Brian A Lindaman1, Marilyn M Hinkhouse, Jeffrey L Conklin
1University of Iowa College of Medicine, Iowa City, 52242, USA.
Background:
Coffee consumption decreases the risk of gallstone disease. The proposed motility effects of caffeine, a phosphodiesterase (PDE) inhibitor, are unknown. The aim of our study was to determine the effect of caffeine and specific PDE inhibitors on gallbladder motility in vitro.
Methods:
Gallbladder muscle strips from opossums were attached to force transducers. Baseline tone, electrical field stimulation (EFS)-induced nitric oxide-mediated off responses, and changes in the cholecystokinin (CCK)-8 dose-response relationship were measured. Caffeine; vinpocetine (VIN), type I PDE inhibitor; erythro-9-[2-hydroxy-3-nonyl]adenine HCl (EHNA), type II PDE inhibitor; zarderverine (ZARD), type III/IV PDE inhibitor; Ro 20-1724, type IV PDE inhibitor; and zaprinast (ZAP), type V PDE inhibitor were added to the tissue baths.
Results:
Caffeine and all specific PDE inhibitors decreased baseline tone. Caffeine, VIN, EHNA, ZARD, Ro 20-1724, and ZAP decreased the EFS-induced off response. Caffeine (10(-5) M) and EHNA increased the CCK-8 dose-response contractions. This effect was not inhibited by atropine. Caffeine increased the tissue levels of cyclic 3',5'-guanosine monophosphate but not cyclic 3',5'-adenosine monophosphate. Caffeine decreases baseline tone and the off response via type I-V PDE pathways. Caffeine also increases CCK-induced gallbladder contractions via type II PDE pathways.
Conclusion:
These effects may be a mechanism that contributes to the decreased gallstone formation with caffeine consumption.
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