Canine renal receptors for parathyroid hormone. Down-regulation in vivo by exogenous parathyroid hormone.
Canine renal receptors for parathyroid hormone. Down-regulation in vivo by exogenous parathyroid hormone.
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犬肾甲状旁腺激素受体。
DOI：
10.1172/jci110989
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Nissenson,RA
中科院分区：
文献类型：
--
作者：
Mahoney,CA;Nissenson,RA
循环甲状旁腺激素（PTH）的慢性升高与靶细胞对PTH的反应性降低有关。为了研究这种现象的亚细胞机制，我们评估了PTH受体和腺苷酸环化酶的活性在肾皮质膜前和后输注牛甲状旁腺提取物（PTE）到甲状腺甲状旁腺切除犬。与配对基线值相比，PTE输注导致高亲和力受体数量减少53%（P <0.01），与PTH刺激的腺苷酸环化酶减少66%（P <0.01）相关。PTH结合的解离平衡常数（KD）和引起腺苷酸环化酶半最大刺激的PTH浓度均在1至4 nM范围内，并且不受PTE输注的影响。肾腺苷酸环化酶对氟化钠的反应性为基线值的88%。单独输注PTE溶剂不影响PTH受体数量或钝化腺苷酸环化酶对PTH的反应。用鸟苷三磷酸（GTP）进行PTE输注后制成的膜进行预处理，这是已知的产生受体结合PTH的解离，未能恢复受体数量或PTH刺激的腺苷酸环化酶。这一发现不是由于缺乏GTP预处理的功效，因为相同的GTP预处理恢复PTH结合基线值在膜部分占据与PTH在体外孵育。因此，PTH受体被输注激素的简单剩余占用似乎不能解释所观察到的受体丢失。这项研究的结果表明，甲状旁腺功能亢进患者的靶细胞对PTH的抵抗可能会发生，至少部分是由于循环激素对PTH受体的下调。
Chronic elevation of circulating parathyroid hormone (PTH) is associated with decreased target cell responsiveness to PTH. To study the subcellular mechanism of this phenomenon we evaluated PTH receptors and adenylate cyclase activity in renal cortical membranes prepared before and after infusion of bovine parathyroid gland extract (PTE) into thyroparathyroidectomized dogs. PTE infusion resulted in a 53% decrease in the number of high-affinity receptors (P less than 0.01) associated with a 66% decrease in PTH-stimulated adenylate cyclase (P less than 0.01) relative to paired base-line values. Both the equilibrium constant of dissociation (KD) for PTH binding and the concentration of PTH that caused half-maximal stimulation of adenylate cyclase were in the range of 1 to 4 nM, and were unaffected by the PTE infusion. Responsiveness of the renal adenylate cyclase to sodium fluoride was 88% of base-line values. Infusion of the PTE vehicle alone did not affect PTH receptor number or blunt the adenylate cyclase response to PTH. Pretreatment of the membranes made after PTE infusion with guanosine triphosphate (GTP), which is known to produce dissociation of receptor-bound PTH, failed to restore either receptor number or PTH-stimulated adenylate cyclase. This finding was not due to a lack of efficacy of the GTP pretreatment, because identical GTP pretreatment restored PTH binding to base-line values in membranes partially occupied by incubation with PTH in vitro. Thus, simple residual occupancy of PTH receptors by the infused hormone did not appear to account for the observed receptor loss. The results of this study suggest that target cell resistance to PTH in patients with hyperparathyroidism might occur, at least in part, due to down-regulation of PTH receptors by circulating hormone.
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甲状旁腺提取物对活动性和愈合性佝偻病血清钙和无机磷酸浓度的影响
DOI：
10.1111/j.1651-2227.1964.tb07216.x
发表时间：
1964
期刊：
Acta Pædiatrica
影响因子：
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作者：
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DOI：
10.1016/s0021-9258(18)93824-x
发表时间：
1964
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
H. Rasmussen;Y. Sze;R. Young
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R. Young
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影响因子：
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DOI：
--
发表时间：
1976
影响因子：
11.1
作者：
D. Schlondorff;H. Weber
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