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.
Persson
P
P
Department of Pharmacology, University of Lund, Sweden.
Håkanson
R
R
Axelson
J
J
Sundler
F
F
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D005743:Gastrectomy; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000502:physiology*; D005755:Gastrins / Q000494:pharmacology*; D006996:Hypocalcemia / Q000209:etiology*; D008297:Male; D010455:Peptides / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D005755:Gastrins; D010455:Peptides; D002118:Calcium