Zinc directly stimulates cholecystokinin secretion from enteroendocrine cells and reduces gastric emptying in rats

• Zinc directly stimulates cholecystokinin (CCK) secretion from CCK-producing cells.
• Extracellular calcium is required for zinc-induced CCK secretion.
• Transient receptor potential ankyrin 1 (TRPA1) mediates zinc-induced CCK secretion.
• Zinc delays gastric emptying through the CCK secretion in rats.

Zinc, an essential mineral element, regulates various physiological functions such as immune responses and hormone secretion. Cholecystokinin (CCK), a gut hormone, has a role in protective immunity through the regulation of gastrointestinal motility, appetite, and inflammatory response. Here, we examined the effect of zinc on CCK secretion in STC-1 cells, an enteroendocrine cell line derived from murine duodenum, and in rats. Extracellular zinc triggered CCK secretion accompanied with increased intracellular Ca2+ and Zn2+ mobilization in STC-1 cells. Zinc-induced CCK secretion was abolished in the absence of intracellular Zn2+ or extracellular calcium. Upon inhibition of transient receptor potential ankyrin 1 (TRPA1), extracellular zinc failed to increase intracellular Ca2+ and subsequent CCK secretion. In rats, oral zinc administration decreased gastric emptying through the activation of CCK signaling. These results suggest that zinc is a novel stimulant for CCK secretion through the activation of TRPA1 related to intracellular Zn2+ and Ca2+ mobilization.