Molecular Biology of Vasoactive Substances

血管活性物质的分子生物学

基本信息

批准号：
06404037
负责人：
NAKAO Kazuwa
金额：
$ 22.21万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

项目摘要

We isolated mouse BNP cDNA and genomic clones, and generated transgenic mice with elevated plasma BNP concentration accompanied with high plasam c GMP concentration. These mice provide a useful model system to assess the roles of BNP.We also isolated hamster BNP and ANP cDNAs to examine pathophysiological roles of natriuretic peptides in cardiomyopathic hamsters. Using cultured rat vascular smmoth muscle cells, we demonstrated that the beta2-adrenergic receptor stimulation duwnregulates the C receptor through the decrease in the transcriptional rate of the C receptor gene and that the activation of sympathetic nervous system augments the biological responsiveness to natriuretic peptides by attenuating their metabolic clearance in vascular walls. The concentration of CNP in the medium was incresed 60 fold in the vascular endothelial cell/vascular smooth muscle cell coculture with direct contact compared with that in endothelial cell alone. We demonstrated that the augmented production of CNP in the coculture is in part regulated by TGF-beta.We isolated two novel transcripts of human endothelin A receptor gene, which contained deletion of exon 4 and 3 and exon 4 resulting from alternative RNA splicing. These transcripts were observed in various human tissues suggesting that this alternative RNA splicing might contribute to the regulation of endothelin A receptor gene expression.We cloned human prostacyclin receptor cDNA and elucidated its abundant gene expression in the cardiovascular system. We also isolated five distinct cDNA clones of human PGE receptor EP_3 subtype and revealed the presence of multiple signal transduction systems of PGE/EP_3 isoform.

我们分离了小鼠 BNP cDNA 和基因组克隆，并产生了血浆 BNP 浓度升高且血浆 c GMP 浓度升高的转基因小鼠。这些小鼠提供了一个有用的模型系统来评估 BNP 的作用。我们还分离了仓鼠 BNP 和 ANP cDNA，以检查钠尿肽在心肌病仓鼠中的病理生理作用。使用培养的大鼠血管平滑肌细胞，我们证明β2-肾上腺素能受体刺激通过降低C受体基因的转录率来调节C受体，并且交感神经系统的激活通过减弱C受体基因的转录率来增强对利尿钠肽的生物反应性。它们在血管壁中的代谢清除。与单独的内皮细胞相比，直接接触的血管内皮细胞/血管平滑肌细胞共培养中培养基中CNP的浓度增加了60倍。我们证明了共培养物中 CNP 的增加部分受到 TGF-β 的调节。我们分离了人内皮素 A 受体基因的两个新转录本，其中包含由于选择性 RNA 剪接而导致的外显子 4 和 3 以及外显子 4 的缺失。在各种人体组织中观察到这些转录本，表明这种替代性 RNA 剪接可能有助于内皮素 A 受体基因表达的调节。我们克隆了人前列环素受体 cDNA，并阐明了其在心血管系统中丰富的基因表达。我们还分离了人 PGE 受体 EP_3 亚型的 5 个不同 cDNA 克隆，并揭示了 PGE/EP_3 亚型的多个信号转导系统的存在。