The Cause and Effect Relationship of Altered Serotonin Signalling in IBS
Serotonin is clearly an important signalling molecule in the activation of motor and secretory reflexes and in the activation of sensory signals from the gut to the CNS. The findings that are described above demonstrate that 5-HT signalling is altered in IBS-D, IBS-C and PI-IBS, but the cause and effect relationship of epigenetic changes in the elements of 5-HT signalling is unclear. In other words, we do not know whether changes in 5-HT signalling contribute to the alterations in GI function and sensation that are the hallmarks of IBS, and/or if elements of 5-HT are altered in response to disrupted function and sensation.
We do not yet know whether 5-HT signalling changes in response to altered gut function, but several lines of evidence support the concept that altered 5-HT signalling can lead to changes in gut function. For example, transgenic mice lacking the gene for SERT typically exhibit symptoms similar to those of IBS-D, but some mice are more similar to IBS-C, as they have decreased colonic motility.[47] In vitro studies involving evaluation of propulsive motility in the guinea-pig distal colon also demonstrate that changes in 5-HT signalling can affect motility. For example, administration of low concentrations of the SSRI, fluoxetine (Prozac), increases the rate of propulsive motility at low concentrations and slows motility at higher concentrations.[40,48] Furthermore, administration of desensitizing concentrations of 5-HT decreases propulsive motility in vivo. These findings support the concept that peristaltic reflex is complicated, and while it can be augmented by slight stimulation, over-stimulation can lead to decreased efficiency, possibly through receptor desensitization in the case of increased 5-HT availability.
Aliment Pharmacol Ther. 2006;23(8):1067-1076. © 2006 Blackwell Publishing
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