Increased gastrin and calcitonin secretion after oral calcium or peptones administration in patients with hypercalciuria: A clue to an alteration in calcium-sensing receptor activity

The calcium-sensing receptor (CaSR) has been detected in human antral gastrin-secreting cells, where, upon calcium and/or amino acid allosteric activation, it stimulates gastrin secretion. Patients with absorptive hypercalciuria (AH) display an enhanced gastric acid output; therefore, we evaluated the secretion of gastrin in subjects with AH ( 30 subjects vs. 30 healthy female controls, all postmenopausal) after oral calcium administration ( 1 g calcium gluconate) and, on a separate occasion, after peptone loading test ( protein hydrolyzed, 10 g). Gastrin and monomeric calcitonin responses were higher in AH after both oral calcium administration ( P < 0.01) and peptone loading ( P< 0.01). Because the activation of CaSR by oral calcium and peptones directly induces gastrin release, the higher gastrin responses to these stimuli suggest an increased sensitivity of gastrin-secreting cells CaSR in patients with AH. A similar alteration in thyroid C cells might explain the enhanced calcitonin responses to both calcium and peptones. If the same alterations should in addition be present in the distal tubule ( where CaSR is expressed as well), then a possible explanation for amino acid-induced hypercalciuria in AH would have been identified.