Calcium-sensing receptor mediates phenylalanine-induced cholecystokinin secretion in enteroendocrine STC-1 cells
Intraluminal l-phenylalanine (Phe) stimulates cholecystokinin (CCK) secretion in vivo and in vitro. However, the cellular mechanism by which CCK-producing enteroendocrine cells sense Phe is unknown. The calcium-sensing receptor (CaR) can sense amino acids, and is expressed in the gastrointestinal tr...
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Published in: | European journal of biochemistry 2008-09, Vol.275 (18), p.4620-4626 |
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Main Authors: | , , , |
Format: | Article |
Language: | eng |
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Online Access: | Get full text |
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Summary: | Intraluminal l-phenylalanine (Phe) stimulates cholecystokinin (CCK) secretion in vivo and in vitro. However, the cellular mechanism by which CCK-producing enteroendocrine cells sense Phe is unknown. The calcium-sensing receptor (CaR) can sense amino acids, and is expressed in the gastrointestinal tract. In the present study, we examined whether CaR functions as a receptor for Phe in CCK-producing enteroendocrine cells. CCK secretion and intracellular Ca²⁺ concentration in response to Phe were measured in the murine CCK-producing enteroendocrine cell line STC-1 at various extracellular Ca²⁺ concentrations or after treatment with a CaR antagonist. At more than 20 m m, Phe induced dose-dependent CCK secretion and intracellular Ca²⁺ mobilization in STC-1 cells. In the presence of 3.0 m m extracellular Ca²⁺, 10 and 20 m m Phe induced significantly higher CCK secretion than under normal conditions (1.2 m m extracellular Ca²⁺). Intracellular Ca²⁺ mobilization, induced by 10 or 20 m m Phe, was also enhanced by increasing extracellular Ca²⁺ concentrations. In addition, intracellular Ca²⁺ mobilization induced by addition of extracellular Ca²⁺ was augmented by the presence of Phe. These results closely match the known CaR properties. Treatment with a specific CaR antagonist (NPS2143) completely inhibited Phe-induced CCK secretion and the latter phase of intracellular Ca²⁺ mobilization. CaR mRNA expression was demonstrated by RT-PCR in STC-1 cells, as well as in other mouse tissues including the kidney, thyroid, stomach and intestine. In conclusion, CaR functions as a receptor for Phe, stimulating CCK secretion in enteroendocrine STC-1 cells. |
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ISSN: | 1742-464X 0014-2956 1742-4658 1432-1033 |