Gastrin releases a blood calcium-lowering peptide from the acid-producing part of the rat stomach.

Gastrin-17 induces hypocalcemia in the rat without stimulating calcitonin release. The gastrin-induced hypocalcemia persisted after thyroparathyroidectomy or parathyroidectomy. In contrast, gastrectomy or extirpation of the acid-producing part of the stomach prevented the hypocalcemic effect, suggesting the involvement of the proximal stomach in the gastrin-evoked lowering of blood calcium. The drop in blood calcium upon injection of gastrin-17 did not reflect a loss of calcium via the gastric juice or via the urine. Extracts of the acid-producing mucosa of the rat stomach had a hypocalcemic effect. The extracts were purified by gel chromatography and reversed-phase high-performance liquid chromatography. Digestion with leucine aminopeptidase destroyed the hypocalcemic activity, while trypsin had no effect, suggesting a peptide (or peptides) with an unprotected NH2 terminus and without basic amino acid residues (or with protected basic amino acids). Both gastrin-17 and the mucosal extract stimulated the uptake of 45Ca into bone (radius and sternum). Gastrin-17 was without effect in rats that had undergone gastrectomy, while the mucosal extract was equally effective in gastrectomized and unoperated rats. We suggest that the effects of gastrin-17 on blood calcium and on calcium transfer into bone are indirect and that gastrin-17 stimulates the release of a peptide hormone, tentatively named gastrocalcin, from the acid-producing mucosa of the stomach. Gastrocalcin stimulates the uptake of 45Ca into bone, thereby causing hypocalcemia.