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bioRxiv · 10.64898/2026.07.15.738825

Oleuropein stimulates peripheral serotonin secretion via voltage-dependent Ca2+ channels and acutely regulates central function

Kamei, Y.·Sugitani, R.·Onzawa, N.·Akao, M.·Fushimi, T.·Akagawa, M.
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Abstract

Serotonin (5-HT) is a monoamine which regulates not only central functions but also various peripheral functions. Peripheral 5-HT is primarily derived from the gut, and its synthesis and secretion are regulated by enterochromaffin cells. Stimulation of enterochromaffin cells by food factors may regulate mental functions via the gut-brain axis. We studied whether oleuropein, an olive-derived polyphenol, regulates central functions by stimulating 5-HT secretion from enterochromaffin cells. In QGP-1 cells, which are enterochromaffin-like cells, 10 {micro}M oleuropein stimulated 5-HT secretion via Ca2+ influx through T-type and L-type voltage-dependent Ca2+ channels. Hydroxytyrosol, a metabolite of oleuropein, also promoted 5-HT secretion via the same mechanism. Furthermore, oleuropein stimulated 5-HT secretion from isolated mouse colon via voltage-dependent Ca2+ channels. Finally, oral administration of 200 mg/kg oleuropein acutely increased the depression-like behavior in the mice, which was inhibited by the prior administration of ramosetron, a 5-HT3 receptor antagonist. These findings suggest that oleuropein is a potent stimulant of gut 5-HT secretion, and show that food factors may act to regulate mental function via the secretion of gut 5-HT.

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Kamei, Y., Sugitani, R., Onzawa, N., Akao, M., Fushimi, T., Akagawa, M.. 2026-07-21. Oleuropein stimulates peripheral serotonin secretion via voltage-dependent Ca2+ channels and acutely regulates central function. https://doi.org/10.64898/2026.07.15.738825

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