5-HT3 receptor expression in primary human monocytes

Abstract

There is evidence that 5-hydroxytryptamine-3 (5-HT3) receptor antagonists may be useful for treatment of inflammatory disorders. Studies from human and animal research showed that 5-HT3 receptor antagonists, particularly tropisetron, exert analgesic and anti-inflammatory activity. We have demonstrated that tropisetron inhibited the release of inflammatory mediators such as tumor necrosis factor (TNF) in primary human monocytes. So far, the underlying mechanisms of these effects have not been investigated in detail. This is especially true for the role of the 5-HT3 receptor subtypes A,B,C,D,E in inflammatory events. Here, we investigated the effects of tropisetron and lipopolysaccharide (LPS) on the expression of 5HT3 receptor A,B,C,D,E mRNA levels by real time PCR and FACS analysis. Our data indicate that the different 5-HT3 receptor subtypes are modulated at its transcriptional and surface expression level by inflammatory conditions and 5-HT3 antagonists such as tropisetron in primary human monocytes. 5-HT3 receptor antagonists are therefore a new and promising therapeutic option. New and more selective – in respect to the 5-HT3 subtypes – 5-HT3R antagonists might be a future perspective in the pharmacological treatment of inflammatory diseases such as rheumatoid arthritis.