The Serotonin System
The serotonin signalling system plays a key role in the modulation of bidirectional gut-brain interactions involved in cognition, emotions, emesis and digestive functions. Although alterations within the serotonin system are assumed to contribute to conditions like Irritable Bowel Syndrome (IBS) and eating disorders, its role in their pathomechanism still
remains enigmatic. Patients often concomitantly suffer from anxiety and depression.
5-HT3 receptor antagonists are beneficial in the treatment of these conditions, but not all patients respond satisfyingly (Walstab et al., 2010a, Niesler, 2011). We therefore hypothesized, that 5-HT3 receptor variants may influence 5-HT3 signalling in the gut-brain axis and thereby modify the susceptibility to both, neurogastrointestinal and psychiatric disorders.
Our research focus comprised the serotonin receptor system in general, with a
special interest in the serotonin type 3 receptor (5-HT3R) diversity and its role
in the aetiology of neuropsychiatric and neurogastrointestinal disorders.
While our efforts to elucidate the heterogeneity of 5-HT3 receptors, we isolated and characterized three novel 5-HT3 (HTR3) genes (Niesler et al., 2003, 2007; Walstab et al., 2010b). Further, we have identified HTR3 variants involved in depression, anxiety, anorexia and IBS as well as in individual drug response, which may serve as pharmacogenetic and biomarkers in the future (Niesler et al., 2001a; Niesler et al., 2001b; Frank et al., 2004;
Kapeller et al., 2008, 2009; Fasching et al., 2008; Hammer et al., 2009;
Hammer et al., 2010; Kilpatrick et al., 2011; Hammer et al., 2012).
To gain further insight into the pathomechanisms of respective disorders and the particular role of 5-HT3 receptors, we established 5-HT3 specific antibodies and confirmed expression of all 5-HT3 receptor subunits in the human gut mucosa and the enteric nervous system, ‘the little brain of the gut’ (Kapeller et al., 2011). In more recent projects, we were able to show that, natural compounds such as ginger, menthol and boldin target 5-HT3A and 5-HT3AB receptors and therefore representing promising options in the treatment of IBS as well as to combat emesis and vomiting (Walstab et al., 2013, 2014).