Impact of the 5-HT3 receptor channel system for insulin secretion and interaction of ginger extracts

The relevance of serotonin and in particular that of 5-HT3 receptors is unequivocal with respect to emetic/antiemetic effects, but it is controversial with respect to antidiabetic effects. The effects of tropisetron (5-HT3 receptor antagonist) and various ginger (Zingiber officinale) extracts (known to interact with the 5-HT3 receptor channel system) were investigated. Serotonin (32 to 500 mu M) inhibits insulin release (RIA) from INS-1 cells which is reversed by tropisetron (10 to 100 mu M) and two different ginger extracts (spissum and an oily extract). Their effects are obvious even in the absence of serotonin but are more pronounced in its presence (doubled to tripled). Specific 5-HT3 binding sites are present in INS-1 cells using 0.4 nM [H-3] GR65630 in displacement experiments. The in vitro data with respect to ginger are corroborated by in vivo data on glucose-loaded rats showing that blood glucose (Glucoquant (R)) is decreased by similar to 35% and plasma insulin (RIA) is increased by similar to 10%. Both the spissum extract and the oily ginger extract are effective in two other models: they inhibit [C-14] guanidinium uptake into N1E-115 cells (model of 5-HT3 effects) and relax rat ileum both directly and as a serotonin antagonistic effect. Other receptors addressed by ginger are 5-HT2 receptors as demonstrated by using methysergide and ketanserin. They weakly antagonize the serotonin effect as well. It may be concluded that serotonin and in particular the 5-HT3 receptor channel system are involved in modulating insulin release and that tropisetron and various ginger extracts can be used to improve a diabetic situation. (C) 2009 Elsevier B.V. All rights reserved.