Håkanson R, Persson P, Axelson J, Johnell O, Sundler F
Department of Pharmacology, University of Lund, Sweden.
Regul Pept. 1990 Mar 27;28(1):107-18. doi: 10.1016/0167-0115(90)90068-8.
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.
胃泌素 - 17的急性刺激使大鼠胸骨和几根长骨对45Ca的摄取增加了约10 - 30%；胃切除术可防止这种效应。用（亮氨酸15） - 胃泌素 - 17长期治疗（通过渗透微型泵持续输注4周）使骨（以桡骨和胸骨为例）对45Ca的摄取增加了18 - 26%（在输注的最后一天进行检测）。手术切除胃的产酸部分（胃底切除术）或用抗溃疡药物雷尼替丁（通过持续输注给予的组胺H2受体拮抗剂）或奥美拉唑（通过胃管每日给予4周的H+/K(+) - ATP酶抑制剂）治疗，可诱导持续性高胃泌素血症（通过胃酸对胃泌素释放的反馈抑制丧失）。雷尼替丁和奥美拉唑引起的高胃泌素血症与骨45Ca摄取增加32 - 62%相关，但胃底切除大鼠的高胃泌素血症并非如此。胃切除术消除了奥美拉唑的作用。我们认为外源性和内源性胃泌素通过从胃的产酸部分释放一种促钙激素（胃钙素）间接影响钙向骨的摄取。胃切除术或胃底切除术（4周）可使骨灰重量降低，但雷尼替丁或奥美拉唑引起的高胃泌素血症（4周）均未提高骨灰重量。用雷尼替丁或奥美拉唑治疗的高胃泌素血症大鼠骨中钙摄取的增加与胫骨中破骨细胞密度增加22 - 32%相关。这一发现符合以下假设，即长期的高胃钙素血症导致骨周转加速而非骨钙含量增加。
