Parathyroid hormone stimulates formation of inositol phosphates in a membrane preparation of canine renal cortical tubular cells.
Parathyroid hormone stimulates formation of inositol phosphates in a membrane preparation of canine renal cortical tubular cells.
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甲状旁腺激素刺激犬肾皮质小管细胞膜制剂中磷酸肌醇的形成。
DOI：
10.1002/jbmr.5650050314
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Bilezikian,JP
中科院分区：
文献类型：
--
作者：
Coleman,DT;Bilezikian,JP
最近的研究表明，除了其众所周知的刺激腺苷酸环化酶活性的作用外，甲状旁腺激素（PTH）还可以刺激其靶组织（骨骼和肾脏）中的磷酸肌醇第二信使系统。我们已经开发了一种犬肾皮质的膜制备来验证这一假设。我们还研究了鸟嘌呤核苷酸在该组织中肌醇磷酸（IP）形成的潜在作用。用[3 H]肌醇标记胶原酶分散的小管，并制备含有标记的磷脂酶C（PLC）底物（[3 H]磷脂酰肌醇、[3 H]磷脂酰肌醇单磷酸和[3 H]磷脂酰肌醇二磷酸）的膜。在刺激的前30 s内，bPTH-（1-34）（100 nM）使所有测量的[3 H] IP（IP 1、IP 2和IP 3）的水平迅速增加1.6-1.7倍。对bPTH-（1-34）的半最大响应浓度约为8 nM。GTPγS（100 μM）是GTP的不可水解类似物，也可增加三种[3 H] IP的水平（1.8至2.8倍）。GTPγS反应的半最大浓度约为30 μM。在存在GTPμS的情况下，bPTH-（1-34）使IP水平增加至单独GTPγS的2.7倍。结果表明，bPTH-（1-34）可以刺激肾脏中磷酸肌醇的形成，并表明PTH可能通过鸟嘌呤核苷酸调节蛋白激活与此作用偶联的受体。
Recent studies have shown that, in addition to its well‐known action to stimulate adenylate cyclase activity, parathyroid hormone (PTH) may stimulate the inositol phosphate second messenger system in its target tissues, bone and kidney. We have developed a membrane preparation of canine renal cortex to test this hypothesis. We also have examined the potential role of guanine nucleotides on the formation of inositol phosphates (IPs) in this tissue. Collagenase‐dispersed tubules were labeled with [3H]inositol, and membranes containing labeled phospholipase C (PLC) substrates ([3H]phosphatidyl inositol, [3H]phosphatidylinositol monophosphate, and [3H]phosphatidylinositol bisphosphate) were prepared. bPTH‐(1–34) (100 nM) rapidly increased levels of all measured [3H]IPs (IP1, IP2, and IP3) 1.6–1.7‐fold within the first 30 s of stimulation. The half‐maximal concentration for the response to bPTH‐(1–34) was approximately 8 nM. GTPγS (100 μM), a nonhydrolyzable analog of GTP, also increased levels of the three [3H]IPs (1.8 to 2.8‐fold). The half‐maximal concentration for the response to GTPγS was approximately 30 μM. In the presence of GTPμS, bPTH‐(1–34) increased levels of IPs by up to 2.7 times more than GTPγS alone. The results indicate that bPTH‐(1–34) can stimulate the formation of inositol phosphates in the kidney and suggest that PTH may activate a receptor coupled to this effect through a guanine nucleotide regulatory protein.