VASOCONSTRICTOR-EVOKED CALCIUM AND LIPID METABOLISM

血管收缩剂引起的钙和脂质代谢

• 批准号: 3345946
• 负责人: AVIV HASSID
• 金额: $ 8.95万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-01 至 1987-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3345946
• 关键词: alpha adrenergic agent; angiotensin /renin /aldosterone hypertension; angiotensin II; eicosanoid metabolism; fatty acid biosynthesis; hormone regulation /control mechanism; lipid metabolism; phosphatidylinositols; radioimmunoassay; thin layer chromatography; vascular smooth muscle; vasoconstriction; vasoconstrictors; vasopressins

I propose to investigate the mechanisms by which vasoconstrictor hormones (angiotensin II, vasopressin, Alpha-adrenergic agents) stimulate calcium and prostaglandin (PG) biosynthesis in cultured rat mesenteric arterial smooth muscle and endothelial cells. The following are specific questions to which answers may be elicited: a) Do vasoconstrictors alter cytosolic calcium levels in cultured cells as measured directly by photoprotein luminescence or fluorescence of intracellular organic calcium indicators? b) What is the role of intracellular and extracellular calcium in hormone-evoked PG biosynthesis? c) What are the effects of vasoconstrictors on the metabolism of phosphatidylinositol, phosphatidic acid and polyphosphoinositides? What is the role of calcium in mediating these changes? d) Does phosphatidic acid function as an endogenous cellular calcium ionophore? e) Do polyphosphoinositides function as endogenous intracellular calcium stores? We expect to use the following analytical techniques to achieve our goals: radioimmunoassay of PGs, measurement of intracellular calcium by a novel technique of aequorin luminescence (or alternatively, measurement of intracellular calcium with the aid of intracellular fluorescent calcium indicators), transmembrane flux of radio-active calcium and radiometric thin-layer chromatography of phospholipids. The results obtained from this research program may increase our understanding of the role played by phospholipids in regulating calcium channels and of the role played by calcium in regulating PG biosynthesis and vasoconstriction.

我建议研究血管收缩激素的机制 （血管紧张素II，加压素，α-肾上腺素能剂）刺激钙 和前列腺素（PG）生物合成培养的大鼠肠系膜动脉 平滑肌和内皮细胞。 以下是特定问题 可能会引起答案：a）做血管收缩剂改变胞质 通过光蛋白直接测量的培养细胞中的钙水平 细胞内有机钙指标的发光或荧光？ b）细胞内和细胞外钙在 激素引起的PG生物合成？ c）有什么影响 磷脂酰肌醇的代谢，磷脂性的血管收缩剂 酸和多磷酸肌醇？ 钙在介导中的作用是什么 这些变化？ d）磷脂酸可以作为内源性 细胞钙离子载体？ e）做py磷酸肌醇的作用 内源性细胞内钙存储？ 我们希望使用以下 实现我们目标的分析技术：PG的放射免疫分析， 通过新型e equorin的技术测量细胞内钙 发光（或替代地测量细胞内钙与 细胞内荧光钙指标），跨膜 放射活性钙和辐射薄层色谱的通量 磷脂。 从该研究计划获得的结果可能 提高我们对磷脂在 调节钙通道和钙在调节中的作用 PG生物合成和血管收缩。