摘要

We previously demonstrated that intraduodenal administration of an arginine-rich beta 51-63 peptide in soybean beta-conglycinin suppresses food intake via cholecystokinin (CCK) secretion in rats. However, the cellular mechanisms by which the beta 51-63 peptide induces CCK secretion remain to be clarified. In the present study, we examined whether the extracellular calcium-sensing receptor (CaR) mediates beta 51-63-induced CCK secretion in murine CCK-producing enteroendocrine cell line STC-1. CCK secretion and changes in intracellular Ca(2+) concentration in response to beta 51-63 peptide were measured in STC-1 cells under various extracellular Ca(2+) concentrations and after treatment with a CaR antagonist. Intracellular Ca(2+) concentrations in response to beta 51-63 peptide and extracellular Ca(2+) were also measured in CaR-expressing human embryonic kidney (HEK-293) cells. The beta 51-63 peptide induced CCK secretion and intracellular Ca(2+) mobilization in STC-1 cells under normal (1.2 mM) extracellular Ca(2+) conditions in a dose-dependent manner. These responses to beta 51-63 peptide were reduced by the removal of intra- or extracellular Ca(2+) but enhanced by increasing extracellular Ca(2+) concentrations. Intracellular Ca(2+) mobilization induced by extracellular Ca(2+) was also increased by the pretreatment with beta 51-63 peptide. Treatment with a specific CaR antagonist (NPS2143) inhibited beta 51-63-induced CCK secretion and intracellular Ca(2+) mobilization. In addition, HEK-293 cells transfected with CaR acquired sensitivity to the beta 51-63 peptide. From these results, we conclude that CaR is the beta 51-63 peptide sensor responsible for the stimulation of CCK secretion in enteroendocrine STC-1 cells.

  • 出版日期2010-1-8