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SOMATOSTATIN BIOSYNTHESIS AND SECRETION

生长抑素生物合成和分泌

基本信息

批准号：
3154459
负责人：
BERNARD A ROOS
金额：
$ 5.23万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-01-01 至 1985-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3154459
关键词：
antiadrenergic agents anticholinergic agent calcitonin eukaryote gel electrophoresis hormone regulation /control mechanism ion transport neural information processing nutrition related tag organ culture peptide hormone biosynthesis peptide hormone metabolism peptides radioimmunoassay radiotracer secretion tissue /cell culture vitamin D

项目摘要

The objective of the proposed studies is to ascertain the separate and combined regulatory effects of endocrine and neural factors on the production and metabolism of calcitonin (CT) and its biosynthetic precursors--procalcitonin (proCT) and a putative prepolcalcitonin (preproCT). For these studies we will employ in vitro preparations of functional C-cells, including organ cultures, suspension cultures, and long-lived monolayer cultures. Our preliminary investigations have shown these C-cell preparations to be exceptionally well suited for regulatory studies of both production and secretion of CT. For instance, we have noted regulatory actions and interactions of enteric polypeptide hormones and vitamin D metabolites and adrenergic and cholinergic agonists on CT production and secretion. Our studies will characterize the separate and combined effects of many neural and endocrine factors on CT secretion and production. We will determine the acute and/or chronic effects of individual and combined regulatory factors on the rates of synthesis, of cleavage, and of degradation of CT, proCT, and preproCT. Relative changes in the rates of these processes will be studied by pulse, pulse-chase, and double-label radioisotopic techniques. Immunoextracted radiolabeled CT moieties chromatography. Regulatory effects on the concentrations of specific CT moieties will be assessed by radioimmunoassay. Effects on the rates of production, cleavage, and/or degradation of CT, proCT, and preproCT will be assessed by incorporation and by decay of radioactivity in specific CT moieties. Understanding the individual and combined regulatory effects of endocrine and neural factors on the rates of synthesis and proteolysis of specific CT moieties will illuminate the metabolic basis for the multifactorial regulation of polypeptide biosynthesis and secretion in eukaryotic cells.

拟议研究的目标是确定独立和合并的内分泌和神经因素对生产和生产的调节作用降钙素及其生物合成前体--降钙素原的代谢 (ProCT)和推测的降钙素原(PreproCT)。对于这些研究，我们将使用功能性C细胞的体外准备，包括器官培养，悬浮培养和长寿单层培养。我们的预赛研究表明，这些C细胞制剂的效果格外好适用于CT的产生和分泌的调节研究。为例如，我们已经注意到肠道病毒的调节作用和相互作用多肽激素和维生素D代谢物与肾上腺素能和胆碱能 CT产生和分泌的激动剂。我们的研究将描述多种神经和内分泌因素对CT的单独和联合影响分泌和生产。我们将确定急性和/或慢性影响单独的和联合的调节因素对合成的速率，卵裂，以及CT、ProCT和PreProCT的退化。中的相对变化这些过程的速率将通过脉冲、脉冲追逐和双标记放射性同位素技术。免疫提取的放射性标记CT部分层析法。对特异性CT浓度的调节作用部分将通过放射免疫测定法进行评估。对利率的影响 CT、ProCT和PreProCT的产生、分裂和/或降解将是通过掺入和特定CT部分的放射性衰变来评估。了解内分泌和内分泌的单独和联合调节作用神经因素对特定CT部分的合成和蛋白分解速率的影响将阐明多因素调节的代谢基础真核细胞中多肽的生物合成和分泌。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Biosynthesis of calcitonin gene-related peptide and calcitonin by a human medullary thyroid carcinoma cell line.

人甲状腺髓样癌细胞系降钙素基因相关肽和降钙素的生物合成。

DOI：
发表时间：
1986
期刊：
The Journal of biological chemistry
影响因子：
0
作者：
Gkonos,PJ;Born,W;Jones,BN;Petermann,JB;Keutmann,HT;Birnbaum,RS;Fischer,JA;Roos,BA
通讯作者：
Roos,BA

Differential alterations of the circulating prosomatostatin-derived peptides during insulin-induced hypoglycemia in man.

胰岛素诱导的人类低血糖期间循环原生长抑素衍生肽的差异变化。