Phenylalanine and tryptophan stimulate gastrin and somatostatin secretion and H+-K+-ATPase activity in pigs through calcium-sensing receptor

In rodents and humans, aromatic amino acids increase gut hormone secretion and H+-K+-ATPase activity by modulating calcium-sensing receptor (CaSR). However, the role of CaSR and its related signaling molecules in amino acid-induced gut hormone secretion in swine has not been investigated. Here, we examined whether a CaSR-dependent pathway modulated gastrin and somatostatin (SS) secretion and H+-K+-ATPase activity in pigs. Perfusion of pig stomach tissues in the presence of extracellular 80 mM l-phenylalanine (Phe) or 20 mM l-tryptophan (Trp) and a CaSR agonist cinacalcet triggered gastrin and SS secretion and H+-K+-ATPase activity (P < 0.05) and increased CaSR expression (P < 0.05). This effect of Phe and Trp was dependent on Ca2+ (P < 0.05) and was abolished after treatment with NPS 2143, an inhibitor of CaSR, and 2-aminoethyl diphenyl borinate, an inhibitor of CaSR downstream signaling molecule inositol 1,4,5-triphosphate receptor (IP3R). These findings indicate that Phe and Trp induce Ca2+-dependent gastrin and SS secretion and H+-K+-ATPase activity through CaSR and its downstream signaling molecule IP3R.