Impact of the 5-HT 3 receptor channel system for insulin secretion and interaction of ginger extracts

Abstract

The relevance of serotonin and in particular that of 5-HT 3 receptors is unequivocal with respect to emetic/antiemetic effects, but it is controversial with respect to antidiabetic effects. The effects of tropisetron (5-HT 3 receptor antagonist) and various ginger ( Zingiber officinale) extracts (known to interact with the 5-HT 3 receptor channel system) were investigated. Serotonin (32 to 500 µM) inhibits insulin release (RIA) from INS-1 cells which is reversed by tropisetron (10 to 100 µM) 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-HT 3 binding sites are present in INS-1 cells using 0.4 nM [ 3H] 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 ®) is decreased by ~ 35% and plasma insulin (RIA) is increased by ~ 10%. Both the spissum extract and the oily ginger extract are effective in two other models: they inhibit [ 14C] guanidinium uptake into N1E-115 cells (model of 5-HT 3 effects) and relax rat ileum both directly and as a serotonin antagonistic effect. Other receptors addressed by ginger are 5-HT 2 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-HT 3 receptor channel system are involved in modulating insulin release and that tropisetron and various ginger extracts can be used to improve a diabetic situation.