Zinc directly stimulates cholecystokinin secretion from enteroendocrine cells and reduces gastric emptying 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 Ca(2+) and Zn(2+) mobilization in STC-1 cells. Zinc-induced CCK secretion was abolished in the absence of intracellular Zn(2+) or extracellular calcium. Upon inhibition of transient receptor potential ankyrin 1 (TRPA1), extracellular zinc failed to increase intracellular Ca(2+) 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 Zn(2+) and Ca(2+) mobilization.
Research Faculty of Health Science, Hokkaido University, Japan; Research Faculty of Agriculture, Hokkaido University, Japan.
Shingo
S
Nakajima
Research Faculty of Agriculture, Hokkaido University, Japan. Electronic address: hira@chem.agr.hokudai.ac.jp.
Tohru
T
Hira
Research Faculty of Agriculture, Hokkaido University, Japan; La Jolla Institute for Allergy & Immunology, USA.
Hitoshi
H
Iwaya
Research Faculty of Agriculture, Hokkaido University, Japan.
Hiroshi
H
Hara
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D002766:Cholecystokinin / Q000097:blood / Q000378:metabolism*; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism*; D005110:Extracellular Space / Q000737:chemistry; D005746:Gastric Emptying / Q000187:drug effects*; D042541:Intracellular Space / Q000737:chemistry; D008297:Male; D051379:Mice; D008954:Models, Biological; D017207:Rats, Sprague-Dawley; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000378:metabolism; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology*
D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D002766:Cholecystokinin; D015032:Zinc
Cholecystokinin; Gastric emptying; Transient receptor potential ankyrin 1 (TRPA1); Zinc