GPR93 activation by protein hydrolysate induces CCK transcription and secretion in STC-1 cells

S Choi, M Lee, AL Shiu, SJ Yo… - American Journal of …, 2007 - journals.physiology.org
S Choi, M Lee, AL Shiu, SJ Yo, G Halldén, GW Aponte
American Journal of Physiology-Gastrointestinal and Liver …, 2007journals.physiology.org
In the intestinal lumen, protein hydrolysate increases the transcription and release of
cholecystokinin (CCK) from enteroendocrine cells of the duodenal-jejunal mucosa. Our
recent discovery that a G protein-coupled receptor, GPR93, is activated by dietary protein
hydrolysate causing induced intracellular calcium-mediated signaling events in intestinal
epithelial cells raises a possibility that GPR93 might be involved in the protein hydrolysate
induction of CCK expression and/or secretion. Using the enteroendocrine STC-1 cells as a …
In the intestinal lumen, protein hydrolysate increases the transcription and release of cholecystokinin (CCK) from enteroendocrine cells of the duodenal-jejunal mucosa. Our recent discovery that a G protein-coupled receptor, GPR93, is activated by dietary protein hydrolysate causing induced intracellular calcium-mediated signaling events in intestinal epithelial cells raises a possibility that GPR93 might be involved in the protein hydrolysate induction of CCK expression and/or secretion. Using the enteroendocrine STC-1 cells as a model, the present study demonstrates that increasing expression of GPR93 amplifies the peptone induction of endogenous CCK mRNA levels. A similar increase in CCK transcription, indicated by the luciferase reporter activity driven by an 820-bp CCK promoter, is also observed in response to peptone at a dose as little as 6.25 mg/ml, but not to lysophosphatidic acid (LPA), an agonist of GPR93. We discovered that the upregulation of CCK transcription involves ERK1/2, PKA, and calmodulin-dependent protein kinase-mediated pathways. Additionally, GPR93 activation by peptone induces a response in CCK release at 15 min, which continues over a 2-h period. The cAMP level in STC-1 cells overexpressing GPR93 is induced at a greater extent by peptone than by LPA, suggesting a possible explanation of the different effects of peptone and LPA on CCK transcription and secretion. Our data indicate that GPR93 can contribute to the observed induction of CCK expression and secretion by peptone and provide evidence that G protein-coupled receptors can transduce dietary luminal signals.
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