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).

FURTHER INFORMATION

International Union of Basic and Clinical Pharmacology -IUPHAR

International Society for Serotonin Research - ISSR

FUNDING BODIES

DFG

Deutsche Krebshilfe

 

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