Inhibition of 5-hydroxytryptamine re-uptake impairs human gall-bladder emptying

SUMMARY Background: 5-Hydroxytryptamine (5-HT) is an important neurotransmitter in the enteric nervous system. The intrinsic neural plexus of the gall-bladder resembles the enteric nervous system and similarly contains 5-HT neurones. The action of 5-HT on gallbladder motility has been investigated in animals but its effect on the human gall-bladder in vivo is unknown. Methods: The effect of indirect 5-HT agonism using paroxetine, a specific inhibitor of neuronal 5-HT reuptake, on gall-bladder motility was investigated in 12 healthy volunteers. In a randomized double-blind crossover design, gall-bladder motility was assessed after administration of 30 mg paroxetine daily for two days and after placebo. Ultrasonography was used to determine gall-bladder volumes while fasting and at 5 min intervals following a 250 kcal mixed liquid meal. Results: Fasting gall-bladder volumes of 21.8 ± 3.2 ml on placebo and 28.0± 3.5 ml on paroxetine were similar. Paroxetine impaired postprandial gall-bladder emptying. Residual gall-bladder volume was 10.2 ±2.7 ml with placebo and 17.1±2.7 ml with paroxetine (P < 0.05). Ejection fraction was 57.3 ±7.7% on placebo and 40.9 ± 4.7% on paroxetine (P < 0.05). Conclusion: 5-HT pathways may participate in the regulation of biliary motility, and this study demonstrates an inhibitory role of 5-HT in the control of human gall-bladder emptying.