ATP DEPENDENCY OF SIGNAL GENERATION AND SECRETION IN RAT BASOPHIL LEUKEMIC CELLS

大鼠嗜碱性粒细胞白血病细胞信号产生和分泌的 ATP 依赖性

• 批准号: 3966548
• 负责人: T N LO
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 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/3966548
• 关键词: adenosine triphosphate; antigens; basophils; calcium; cell cell interaction; chemical stimulation; dosage; histamine release; mouse leukemia; neoplastic cell; phosphatidylinositols; phosphorylation; secretion

Rat leukemic basophil (2H3) cell line was stimulated to secrete histamine either with calcium-specific ionophores or by aggregation of plasma membrane receptors for IgE. The ionophore, A23187, at concentrations (less than 100 nM) well below those stimulating secretion elicited large increases in (Ca2+)i and at higher concentrations (200-1000nM) stimulated hydrolysis of membrane radiolabeled inositol phospholipids as well. The hydrolysis was dependent on the concentration of ionophore and presence of external Ca2+ and was correlated with the secretory response. The results pointed to generation of diacylglycerol rather than of inositol phosphates as a critical factor in the action of A23187. When secretory responses were plotted as a function of percent hydrolysis of inositol phospholipid, the curve was shifted leftwards in the presence of the phorbol ester, TPA, which, like diacylglycerol, is an activator of protein kinase C. Paradoxically, the increases in (Ca2+)i in response to both antigen and A23187 were highly dependent on intracellular ATP levels.

刺激大鼠白血病嗜碱性粒细胞（2H3）细胞系分泌组胺 通过钙特异性离子载体或通过血浆聚集 IgE 的膜受体。 离子载体，A23187，浓度（小于 低于 100 nM）远低于那些刺激分泌引起大量 (Ca2+)i 的增加和更高浓度 (200-1000nM) 的刺激 膜放射性标记肌醇磷脂的水解。 这 水解取决于离子载体的浓度和存在 外部 Ca2+ 并与分泌反应相关。 结果 指出生成二酰基甘油而不是磷酸肌醇 作为 A23187 作用的关键因素。 当分泌反应 绘制为肌醇磷脂水解百分比的函数， 在佛波酯 TPA 存在的情况下，曲线向左移动， 与二酰甘油一样，它是蛋白激酶 C 的激活剂。 矛盾的是，(Ca2+)i 响应抗原和 A23187 高度依赖于细胞内 ATP 水平。