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

Abstract

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.

Vitamin D substrate–product relationship in idiopathic hypercalciuria

“…Patients were randomly selected during wintertime from November 2005 to March 2006 from those attending our clinic in the context of an ongoing program of evaluation of bone and nutritional status of postmenopausal women in Northern Milan, Italy [25,26] and from men with urolithiasis referred to us for evaluation of related bone and metabolic diseases. One hundred and sixty one subjects with AH and renal stone disease (45-75 years old; mean ± SD age: 60.9 ± 11.7 years) were evaluated as well as 110 age and sexmatched controls (45-76 years old; mean ± SD: 61.5 ± 12.4 years).…”

Effects of cinacalcet on gastrointestinal hormone release in patients with secondary hyperparathyroidism undergoing dialysis

“…Each column represents the mean ± SEM. [33][34][35]. Furthermore, the calcimimetic compound KRN568 increased gastrin release in healthy subjects [36].…”

Calcium-sensing receptor 20 years later

“…The activation of CaSR and in turn increased acid secretion may explain this observation. In this context, modulation of gastric acid secretion by targeting CaSR on acid-secreting cells as well as neighboring G and enterochromaffin-like (ECL) cells is theoretically feasible (6,38). In most cases the acid secretion should be decreased and this entails the inhibition of CaSR by calcilytics (38,50).…”