MECHANISMS OF UPTAKE OF NOREPINEPHRINE IN ADRENERGIC STORAGE VESICLES IN SITU

肾上腺素能储存囊泡原位摄取去甲肾上腺素的机制

• 批准号: 3966600
• 负责人: D F BOGDANSKI
• 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/3966600
• 关键词: 2,4 dinitrophenol; adenosinetriphosphatase; chlorine; electrochemistry; imines; ion transport; magnesium; maleimides; membrane permeability; nerve endings; neuropharmacology; norepinephrine; phosphatase inhibitor; secretion; synaptic vesicles

Biochemical evidence has been adduced to support the hypothesis that adrenergic neurosecretion can be mediated by the outward transport of norepinephrine (NE) from synaptic vesicles that are fused or attached to the plasma membrane of the nerve ending. Moreover, theories of uptake and retention of NE by isolated vesicles incubated in sucrose-based media seem to be verified by our experiments in which the vesicles are located within the nerve endings in heart ventricle slices in vitro. The results suggest that a driving force for the uptake and retention of NE by vesicles is the electro-chemical gradient of H+ established by the activity of Mg-ATPase. However, these effects of Mg-ATPase activity in situ occur in the presence of high concentrations of C1-. In isolated vesicles incubated in sucrose with ATP, C1-inhibits uptake and induces lysis of vesicles. The uptake of NE by vesicles in situ is blocked by Li+, N-ethylmaleimide (NEM), and Dicyclohexylcarbodiimide (DCCD) which are all inhibitors of Mg-ATPase. Uptake is also inhibited by 2,4-dinitrophenol (2,4-DNP) a dissipator of H+ electrochemical gradients, (NH4)2S04 which neutralizes an established pH gradient across the vesicle membrane, and nigericin, which facilitates an electrically neutral exchange of H+ and K+ across the membrane. Apparently, non-exocytotic secretion can occur in the presence of physiological concentrations of C1-.

生物化学证据已被引用来支持这一假设