Evidence that gastrin enhances 45Ca uptake into bone through release of a gastric hormone.
An acute challenge with gastrin-17 enhanced the uptake of 45Ca into sternum and several long bones in rats by about 10-30%; gastrectomy prevented this effect. Long-term treatment with (Leu15)-gastrin-17 (continuous infusion via osmotic minipumps for 4 weeks) enhanced the uptake of 45Ca into bone (examplified by radius and sternum) by 18-26% (tested on the last day of the infusion). Surgical removal of the acid-producing part of the stomach (fundectomy) or treatment with the anti-ulcer drugs, ranitidine (a histamine H2-receptor antagonist administered by continuous infusion) or omeprazole (an H+/K(+)-ATPase inhibitor administered daily by gastric tube for 4 weeks), induced sustained hypergastrinemia (through loss of acid feedback inhibition of gastrin release). The ranitidine- and omeprazole-evoked hypergastrinemia was associated with 32-62% enhancement of bone 45Ca uptake but the hypergastrinemia of fundectomized rats was not. Gastrectomy abolished the effect of omeprazole. We suggest that exogenous and endogenous gastrin influences calcium uptake into bone indirectly by releasing a calciotropic hormone (gastrocalcin) from the acid-producing part of the stomach. The bone ash weight was reduced by gastrectomy or fundectomy (4 weeks), but neither ranitidine nor omeprazole-evoked hypergastrinemia (4 weeks) raised the bone ash weight. The stimulated calcium uptake into bone of hypergastrinemic rats treated with ranitidine or omeprazole was associated with a 22-32% increase in the density of osteoclasts in the tibia. This finding is in line with the hypothesis that long-lasting hypergastrocalcinemia produces accelerated turn-over of bone rather than increased bone calcium content.
Håkanson
R
R
Department of Pharmacology, University of Lund, Sweden.
Persson
P
P
Axelson
J
J
Johnell
O
O
Sundler
F
F
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D005260:Female; D005743:Gastrectomy; D005755:Gastrins / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D011863:Radioimmunoassay; D011884:Radius / Q000187:drug effects / Q000378:metabolism; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013249:Sternum / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D005755:Gastrins; C013550:gastrin 17; D011899:Ranitidine; D009853:Omeprazole; D002118:Calcium