Hyperparathyroidism and cellular mechanisms of gastric acid secretion

Patients with hyperparathyroidism appear to be a particular risk for peptic ulcer disease. To test the hypothesis that hypercalcemia or parathyroid hormone plays a role in promoting ulcer disease, we studied the effect of varying concentrations of extracellular calcium on acid secretion using in vitro isolated rabbit gastric glands. Acid secretion was assessed by the accumulation of carbon 14-labeled aminopyrine (14C-AP). Glands were incubated with varying calcium concentrations in the unstimulated state and with histamine or carbachol (10(-7) to 10(-4) mol/L) in 1 or 2 mmol/L calcium medium. The effect of parathyroid hormone was also examined under identical conditions. Compared to 1 mmol/L standard calcium medium, unstimulated 14C-AP accumulation was significantly inhibited (p less than 0.05) at both lower (0.33 mmol/L) and higher (2 and 2.5 mmol/L) calcium concentrations. Accumulation of 14C-AP in response to histamine stimulation was unaffected by alteration of extracellular calcium (p greater than 0.2). Carbachol-stimulated 14C-AP accumulation was significantly augmented (p less than 0.01) by an increase in calcium concentration from 1 to 2 mmol/L. The addition of parathyroid hormone (10(-7) to 10(-4) mmol/L) alone or in combination with carbachol or histamine (10(-6) mmol/L) incubation did not alter 14C-AP accumulation. These data suggest that elevations in extracellular calcium play an active role in the potentiation of cholinergic-mediated gastric gland acid secretion and may thereby play a role in hyperparathyroid-related ulcer disease.