Effects of a synthetic peptide of a parathyroid hormone-related protein on calcium homeostasis, renal tubular calcium reabsorption, and bone metabolism in vivo and in vitro in rodents.
Effects of a synthetic peptide of a parathyroid hormone-related protein on calcium homeostasis, renal tubular calcium reabsorption, and bone metabolism in vivo and in vitro in rodents.
复制标题
甲状旁腺激素相关蛋白的合成肽对啮齿动物体内和体外钙稳态、肾小管钙重吸收和骨代谢的影响。
DOI：
10.1172/jci113406
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Mundy,GR
中科院分区：
文献类型：
--
作者：
Yates,AJ;Gutierrez,GE;Smolens,P;Travis,PS;Katz,MS;Aufdemorte,TB;Boyce,BF;Hymer,TK;Poser,JW;Mundy,GR
本文研究了与高钙血症相关的人肿瘤产生的甲状旁腺相关蛋白（PTH-rP）的前34个氨基酸对应的合成肽在体内和体外对骨骼和肾脏钙代谢的影响。并与人甲状旁腺素（1-34）、hPTH（1-34）进行了比较。在体外，相同剂量的PTH-rP（1-34）和hPTH（1-34）在骨细胞、肾细胞和肾小管中产生等同的腺苷酸环化酶刺激。小鼠皮下注射PTH-rP（1-34）引起血液离子钙的显著剂量相关性增加，与同等剂量的hPTH（1-34）相似。重复注射相同剂量的两种肽引起持续的高钙血症，这在PTH-rP（1-34）治疗的小鼠中显著更高，尽管每种肽都诱导了骨细胞骨吸收的组织形态计量学指数的相当增加。PTH-rP（1-34）和hPTH（1-34）在与器官培养中的胎鼠长骨一起孵育时也引起类似的骨吸收增加。向甲状腺甲状旁腺切除大鼠输注任一肽抑制尿钙排泄并增加尿cAMP排泄。PTH-rP似乎与PTH对骨骼、肾脏和整体钙稳态的影响相似。图片
A synthetic peptide corresponding to the first 34 amino acids of the parathyroid hormone-related protein (PTH-rP) produced by a human tumor associated with hypercalcemia was examined for skeletal and renal effects on calcium metabolism in vivo and in vitro. These effects were compared with those of human parathyroid hormone (1-34), hPTH (1-34). Equal doses of PTH-rP(1-34) and hPTH(1-34) produced equivalent stimulation of adenylate cyclase in vitro in bone cells and kidney cells and tubules. Subcutaneous injection of PTH-rP(1-34) in mice caused a significant dose-related increase in blood ionized calcium similar to that seen with hPTH(1-34) at equivalent doses. Repeated injections of equal doses of both peptides caused sustained hypercalcemia which was significantly greater in PTH-rP(1-34)-treated mice, although each induced comparable increases in histomorphometric indices of osteoclastic bone resorption. PTH-rP(1-34) and hPTH(1-34) also caused similar increases in bone resorption when incubated with fetal rat long bones in organ culture. Infusion of either peptide into thyroparathyroidectomized rats suppressed urinary calcium excretion and increased urinary excretion of cyclic AMP. PTH-rP appears to have similar effects to those of PTH on the skeleton, the kidney, and overall calcium homeostasis.Images