SODIUM-DEPENDENT SECRETION AND RETENTION OF NE IN ADRENERGIC TERMINALS

肾上腺素能末梢中钠依赖的 NE 分泌和保留

• 批准号: 3879002
• 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/3879002
• 关键词: adenosine triphosphate; adrenergic receptor; amination; axon; cations; drug metabolism; hypertension; laboratory rat; lithium; norepinephrine; secretion; sodium; synaptic vesicles

Mechanisms for both Na+-dependent hypertension and the therapeutic effect of Li+ are not known. This report supports the hypothesis that Na regulates the secretion and recapture of NE from a pool of mobile amine in adrenergic terminals in rat heart slices. Lithium produces a functional deficiency of Na. Mobilized NE was accumulated in terminals as a result of metabolic deficiencies during the overnight dialysis of terminals in solutions of either Na, K, Li or choline at 0 degrees. The axolemma was the dialysis membrane. The mobilized NE was depleted during a subsequent incubation of terminals in Krebs medium (KRB) at 37 degrees. The rapidly induced depletion was independent of the primary dialysis cation, and, the presence of Ca in the KRB. Depletion was inhibited by either dialyzed (intraterminal) ATP or import export blockers such as cocaine. These agents in the incubation medium were not inhibitory. The depletion of mobile NE differed from the secretion of vesicular NE. Forty percent of the remaining NE was stably retained in synaptic vesicles. Secretion from vesicles was evoked by the incubation of terminals in a Na-deprived (Choline) KRB (Ch-Ca). Secretion was delayed, dependent upon intraterminal Na, and, Ca in the medium. Secretion was mediated by export from a previously described vesicular-axolemmal secretory and transmitter recovery unit comprised of vesicles whose membranes had fused with the axolemma. Bound intravesicular NE was mobilized in the process then exported. The vesicle membrane was accessible to ATP in the medium. In non-dialyzed terminals, secretion was inhibited by ATP only when Na was present. Thus, Na was required for the translocation of NE into and out of terminals. Lithium, in a therapeutic concentration of I mM prevented the vesicle from recapturing released or mobilized NE. This effect was indicated by an increased deamination of NE. Thus, Li appeared to interfere with a requirement for Na in the recapture process in an active unit. On the basis of published reports, Li may act by inhibiting Mg-ATPase activity and dependent NE uptake in isolated synaptic vesicles. The present report adds the important information that Li can act in therapeutic concentrations on vesicles in situ. Since Li stimulates deamination in rat brain in vivo, the postulated role for Na may be relevant therapeutically.

钠离子依赖性高血压的机制及治疗效果 Li+是未知的。这份报告支持Na调节的假设， 肾上腺素能神经元从移动的胺池中分泌和重新捕获NE 大鼠心脏切片中的终末。锂会导致 Na.代谢产物NE在终末聚集， 在终末的过夜透析过程中， Na，K，Li或胆碱在0度。轴膜就是透析 膜的在随后的孵育过程中，动员的NE被耗尽。 终端在克雷布斯培养基（KRB）中，温度为37度。快速诱导 消耗与主要透析阳离子无关， KRB中的Ca。无论是透析还是透析， （终端内）ATP或输入输出阻滞剂，如可卡因。这些试剂 在孵育介质中没有抑制作用。移动的NE的耗尽 与泡状NE分泌不同。剩下的百分之四十 NE稳定地保留在突触囊泡中。囊泡分泌物为 在Na剥夺（胆碱）KRB中终末孵育诱发的 （Ch-Ca）。分泌延迟，依赖于终末内钠，钙， 媒介分泌是通过从先前描述的 囊泡-轴膜分泌和递质恢复单位，包括 膜与轴膜融合的囊泡。囊内结合 NE在此过程中被调动，然后输出。囊泡膜为 ATP在介质中。在非透析终末， 只有当Na存在时才被ATP抑制。因此，需要Na NE进出末梢的易位。锂，在治疗中 ImM的浓度防止囊泡重新捕获释放的或 动员了。这一作用表现为NE脱氨作用的增加。 因此，李似乎干扰了一个要求纳在夺回 在一个活跃的单位。根据已公布的报告，李可采取以下行动： 抑制突触Mg-ATP酶活性和依赖性NE摄取 囊泡本报告增加了李能行事的重要信息 在囊泡上的治疗浓度。由于李刺激 在体内大鼠脑中的脱氨作用，Na的假定作用可能是 治疗相关。