TRANS-SYNAPTIC CONTROL OF THE CA2+/PHOSPHOLIPID-DEPENDENT PROTEIN KINASE

CA2/磷脂依赖性蛋白激酶的跨突触控制

• 批准号: 4696400
• 负责人: B WISE
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4696400
• 关键词: adrenal medulla; brain cell; calcium; catecholamines; chromaffin cells; enzyme substrate; glutamates; inositol phosphates; membrane activity; membrane permeability; neurophysiology; phorbols; phosphatidylinositols; phospholipids; protein kinase C; radioimmunoassay; receptor mediated endocytosis; synapses; tissue /cell culture

The Ca2+/phospholipid dependent protein kinase (protein kinase C) is an important intracellular mediator of the actions of extracellular signals that stimulate the breakdown of phosphatidylinositol to inositol phosphate and diacylglycerol. Diacylglycerol may be the second messenger, analogous to cAMP, that directly activates protein kinase C. The potential involvement of this enzyme in the functioning of adrenal chromaffin cells and cerebellar granule cells was the subject of this research project. Protein kinase C is present in bovine adrenal medulla and its constituent chromaffin cells in significant amounts compared to other tissue. In membranes and cytosol of the medulla, there are several specific endogenous substrate proteins for the enzyme. Treatment of primary cultures of chromaffin cells with phorbol esters, drugs which can substitute for diacylglycerol in the in vitro and in vivo activation of the enzyme, induce an apparent translocation of soluble enzyme activity to a membrane associated form. This translocation is specific for those phorbol esters that can activate the enzyme in vitro. Concomitant with the translocation of the enzyme activity is a significant phorbol ester induced release of catecholamines. Receptor-dependent activation of protein kinase C in cerebellar granule cells is also under study. Preliminary results indicate that glutamate, which stimulates phosphatidylinositol turnover in these cells, causes an approximate 20 to 30% increase in membrane-associated enzyme activity. The above studies indicate a potential prominent role for protein kinase C in chromaffin cells and cerebellar granule cells and that the receptor dependent activation of the enzyme may be manifested as a translocation of enzyme activity from cytosol to membrane.

Ca 2 +/磷脂依赖性蛋白激酶（蛋白激酶C）是一种蛋白激酶。 细胞外信号作用的重要细胞内介质 刺激磷脂酰肌醇分解为磷酸肌醇 和二酰基甘油。 甘油二酯可能是第二信使， 转化为cAMP，直接激活蛋白激酶C。 的潜在 这种酶参与肾上腺嗜铬细胞的功能 和小脑颗粒细胞是本研究项目的主题。 蛋白激酶C存在于牛肾上腺髓质及其成分中， 与其他组织相比，嗜铬细胞数量显著增加。 在 在髓质的细胞膜和细胞质中，有几种特定的内源性 酶的底物蛋白质。 原代培养物的处理 嗜铬细胞与佛波醇酯，药物，可以取代 甘油二酯在体外和体内激活酶，诱导 可溶性酶活性明显转移到膜上 关联形式。 这种易位是特定的佛波醇酯 可以在体外激活这种酶 伴随易位 的酶活性是一个显着的佛波酯诱导释放 儿茶酚胺 蛋白激酶C的受体依赖性激活 小脑颗粒细胞也在研究中。 初步结果表明 谷氨酸盐，它刺激磷脂酰肌醇的周转， 细胞，导致大约20%至30%的膜相关的增加， 酶活性 上述研究表明， 嗜铬细胞和小脑颗粒细胞中的蛋白激酶C， 酶的受体依赖性活化可以表现为 酶活性从细胞质向细胞膜的转移。