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Intracellular signal transduction of parathyroid hormone receptor activation and its pathphysiology

甲状旁腺激素受体激活的细胞内信号转导及其病理生理学

基本信息

批准号：
07456129
负责人：
ITO Shigeo
金额：
$ 4.99万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07456129/
关键词：
dog parathyroid hormone PTH receptors cDNA cloning northern blot analysis cyclic AMP smooth muscles intracellular Ca^<2+> concentration whole-cell voltage clamp ノーザンプロット解析パラサイロイドホルモン血管平滑筋細胞内情報伝達

项目摘要

1. In order to deduce the amino acid sequence of dog parathyroid hormone (PTH) receptors, cDNA cloning was carried out using the cDNA library of the liver and kidney. We found that dog PTH receptors were putative G protein-coupled membrane protein having seven membrane spanning domains and that the amino acid sequence of PTH receptors of the dog was homologus that of human (95.3%), rat (88.0%) or opossum (79.1%). The northern blot analysis showed that PTH receptors were expressed in the kidney, liver, brain, aorta and bone marrow. 2. The effect of PTH on contractions and changes in intracellular Ca^<2+> ( [Ca^<2+>] in) was examined in the rat superior mesenteric artery to know the intracellular signal transduction of the PTH receptor activation. PTH inhibited a contraction and increase in [Ca^<2+>] in induced by phenyrephrine greater than that by high concentrations of KCI (high K). PTH inhibited IP3-induced Ca^<2+> release actibated by phenyrephrine without any effects on Ca^<2+>-induced Ca^<2+> release activated by caffeine. PTH decreased a contraction evoked by high K without inhibitory effects on changes in [Ca^<2+>] in, suggesting that PTH has a direct inhibitory effect on the contractile machinery. Intracellular signal trasduction by the PTH receptor may be coupled with increases in cyclic AMP by the activation of the adenylate cyclase. 3. The characteristics of IP3-induced Ca^<2+> release and the source of Ca^<2+> taken up into Ca^<2+> stores were examined in the intestinal smooth muscle. Ca^<2+> released from the store activated not only the contractile machinery but also Ca^<2+>-activated K^+ channels. Ca^<2+> stores seem to take up into Ca^<2+> preferentially passing through unique Ca^<2+> channels, but not voltage-dependent Ca^<2+> channels. PTH may affect the Ca^<2+> release and/or Ca^<2+> uptake through cyclic AMP-dependent pathways.

1.为了推导狗甲状旁腺激素(PTH)受体的氨基酸序列，利用肝脏和肾脏的cDNA文库进行了cDNA克隆。我们发现狗的PTH受体是假定的G蛋白偶联膜蛋白，具有7个跨膜结构域，并且狗的PTH受体的氨基酸序列与人(95.3%)、大鼠(88.0%)或负鼠(79.1%)的同源。 Northern印迹分析显示PTH受体在肾、肝、脑、主动脉和骨髓中表达。 2、检测PTH对大鼠肠系膜上动脉收缩及细胞内Ca^2+([Ca^2+]in)变化的影响，了解PTH受体激活的细胞内信号转导。 PTH对苯肾上腺素诱导的[Ca 2+ ]收缩和增加的抑制作用强于高浓度KCI(高K)诱导的抑制作用。 PTH抑制去氧肾上腺素激活的IP3诱导的Ca 2+ 释放，而对咖啡因激活的Ca 2+ 诱导的Ca 2+ 释放没有任何影响。 PTH 减少了高 K 引起的收缩，但对 [Ca^2+] 的变化没有抑制作用，表明 PTH 对收缩机制具有直接抑制作用。 PTH 受体的细胞内信号转导可能与腺苷酸环化酶激活导致的环 AMP 增加相结合。 3.研究了肠平滑肌中IP3诱导的Ca^2+释放特征以及吸收到Ca^2+储存中的Ca^2+来源。从存储中释放的 Ca^<2+> 不仅激活了收缩机制，而且还激活了 Ca^<2+> 激活的 K^+ 通道。 Ca^<2+>存储似乎优先通过独特的Ca^<2+>通道而不是电压依赖性Ca^<2+>通道吸收Ca^<2+>。 PTH可能通过环AMP依赖性途径影响Ca ^ 2+ 释放和/或Ca ^ 2+ 摄取。