Osteoblast-specific CGRP receptor -expression of osteoblastic differentiation-independent non-type I CGRP receptor-

成骨细胞特异性 CGRP 受体 -成骨细胞分化独立的非 I 型 CGRP 受体的表达 -

基本信息

批准号：
16591855
负责人：
KAWASE Tomoyuki
金额：
$ 2.05万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591855/
关键词：
CGRP osteoblast receptor cell differentiation

项目摘要

1) Effects of CGRP on cytoplasmic Ca^<2+> mobilization and membrane potentialIn human osteoblastic MG63 cells, CGRP (1-100 nM) induced a transient Ca^<2+> spike and a subsequent slow increment in cytoplasmic free Ca^<2+> concentrations ([Ca^<2+>]_i). The second phase was not observed in rat osteoblastic UMR106 cells. CGRP also induced plasma membrane hyperpolarization. This action was attenuated only approximately 50% by an antagonist of CGRP subtype I receptor (CGRP-R1), CGRP_<8-37>. These findings suggest that These CGRP actions are not solely mediated by known CGRP-R1 but also by other non-subtype I receptors.2) Schild plot analysis of CGRP-induced cellular responsesIn MG63 cells, the CGRP-induced cellular responses, such as cAMP production, p38-MAPK phosphorylation, and CREB phosphorylation, were identified to be mediated by the same single CGRP receptor subtype, probably CGRP-R1. In contrast, CGRP-induced ERK dephosphorylation was suggested to be mediated either by a single unknown subtype of CGRP receptor or by a combination of CGRP-R1 and a unknown receptor subtype(s).3) Effects of adrenomedullin, calcitonin, and their specific antagonists on intracellular signaling pathwaysIn addition to MG63 cells, human periodontal ligament cells were employed here. Both adrenomedullin (ADM) and calcitonin (CT) at higher concentrations (1 μM) mimicked CGRP action, but their specific antagonists, such as ADM_<22-52> and CT_<8-32>, failed to significantly block CGRP action. These findings suggest that CGRP actions we have observed are not mediated either by ADM receptor or CT receptor, but by several CGRP-specific receptor subtypes.

1）CGRP OND MEMRBANE势素蛋白成骨细胞MG63细胞，CGRP（1-100 nm）<2+>尖峰和随后的细胞质游离Ca^<2+浓度的慢速增量（[Ca^<2+>]）。在大鼠成骨细胞UMR106细胞诱导的质体ization中未观察到第二相。由已知的CGRP-R1 E I受体介导的Soly。2）CGRP诱导的细胞反应的Schild图分析MG63细胞，CGRP诱导的Cellaru反应，例如CAMP生产，p38-MAPK磷酸化，由同一单个CGRP介导受体亚型，可能的CGRP-R1。细胞以较高浓度（1μM）的含量使用丁蛋蛋白（ADM）和降钙素（CT），但是它们的特定拮抗剂，例如ADM_ <222-52>和CT_ <8-32>，这些发现表明我们意识到的CGRP动作是不是由ADM受体或CT PTOR介导的，而是由几种CGRP特异性受体亚型介导的。