Expression patterns of l-amino acid receptors in the murine STC-1 enteroendocrine cell line

Regulation of gut function depends on the detection and response to luminal contents. Luminal l-amino acids (l-AA) are detected by several receptors including metabotropic glutamate receptors 1 and 4 (mGluR1 and mGluR4), calcium-sensing receptor (CaSR), GPRC family C group 6 subtype A receptor (GPRC6A) and umami taste receptor heterodimer T1R1/T1R3. Here, we show that murine mucosal homogenates and STC-1 cells, a murine enteroendocrine cell line, express mRNA for all l-AA receptors. Immunohistochemical analysis demonstrated the presence of all l-AA receptors on STC-1 with CaSR being most commonly expressed and T1R1 least expressed (35% versus 15% of cells); mGluRs and GPRC6a were intermediate (~ 20% of cells). Regarding coexpression of l-AA receptors, the mGluRs and T1R1 were similarly coexpressed with CaSR (10–12% of cells) whereas GPRC6a was coexpressed least (7% of cells). mGluR1 was coexpressed with GPRC6a in 11% of cells whereas coexpression between other receptors was less (2–8% of cells). CaSR and mGluR1 were coexpressed with glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) in 20–25% of cells whereas T1R1 and GPRC6a were coexpressed with GLP-1 and PYY less (8–12% of cells). Only mGluR4 showed differential coexpression with GLP-1 (13%) and PYY (21%). l-Phenylalanine (10 mM) caused a 3-fold increase in GLP-1 release, which was strongly inhibited by siRNA to CaSR indicating functional coupling of CaSR to GLP-1 release. The results suggest that not all STC-1 cells express (and coexpress) l-AA receptors to the same extent and that the pattern of response likely depends on the pattern of expression of l-AA receptors.