The Effect of Phosphodiesterase Inhibition on Gallbladder Motility in Vitro

Abstract

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.