MECHANISMS OF SECRETION AND RETENTION OF NE IN SYNAPTIC VESICLES IN AXOPLASM

本实验室研究了去甲肾上腺素(NE)的摄取和滞留。 在肾上腺素能神经轴浆(原位)的突触小泡中 终末在体外。当大鼠的心脏切片在 去钠(12.5~25mM Na，胆碱)Krebs-小苏打培养液 (CH+-Ca++)、突触小泡和轴膜似乎建立了一种新的 能分泌储存的NE和重新捕获NE的形态单位 5~6成熟。这个实验室是第一批发现这种电子的实验室之一。 运输可能与滞留有关。分泌物是由 轴膜上的胺泵和再捕获是由 囊泡膜。在这种准备过程中，后者依赖于 外源三磷酸腺苷。Mg++-ATPase抑制滞留和重新捕获 抑制剂，K+-H+交换离子载体，H+离子载体和利血平，它们 阻断泡泡膜中的NE泵。这些抑制剂都是已知的 阻断依赖于H+转运的摄取，所述H+转运由 囊泡膜中的Mg++-ATPase。此外，摄取和保留是 被氨水阻止。结论是，吸收和滞留在 原位的囊泡由一个pH梯度，即跨 囊泡膜(Bogdanski，1982,1983,1986,1988)。 这些发现具有重要的生理学意义。同样的抑制剂可以防止 去甲肾上腺素在KRB孵化终末的滞留。Mg~(++)和Mn~(++)阻断 钙离子在神经末梢的电压依赖性进入(Blaustein)。镁++区块 在体囊泡钙离子内流和去甲肾上腺素耗竭。Mn++嵌段胺 特别是分泌物。脱氨基代谢物的排泄不是 被禁止了。看来，钙离子在人体内起着类似的作用 体内分泌和原位囊泡分泌。分泌不是由 胞吐。 囊泡与轴外膜的融合受Na+的控制。端子位于 如果完全省略了Na+，则CH+-CA+不对ATP作出响应 5~6成熟。锂能抑制Na+依赖。

This laboratory has studied the uptake and retention of norepinephrine (NE) in synaptic vesicles in the axoplasm (in situ) of adrenergic nerve terminals in vitro. When slices of rat heart ventricle are incubated in a Na+-deprived (12.5 to 25muM Na, choline) Krebs-bicarbonate medium (Ch+-Ca++), synaptic vesicles and axolemma appear to establish a new morphological unit which can secrete stored NE and recapture NE in the medium. This laboratory was among the first to recognize that electron transport could be involved in retention. Secretion is mediated by the amine pump in the axolemma and recapture is mediated by the amine pump in the vesicle membrane. In this preparation, the latter is dependent upon exogenous ATP. Retention as well as recapture are inhibited by Mg++-ATPase inhibitors, K+-H+ exchange ionophores, H+ ionophores and reserpine, which blocks the NE pump in the vesicle membrane. These inhibitors are all known to block uptake dependent upon H+ transport energized by the activity of Mg++-ATPase in the vesicle membrane. Furthermore, uptake and retention are prevented by ammonia. It was concluded that uptake and retention in vesicles in situ are energized by a pH gradient, delta pH, across the vesicle membrane (Bogdanski, 1982,1983,1986,1988). These findings are physiologically significant. The same inhibitors prevent the retention of NE in incubated terminals in KRB. Mg++ and Mn++ block the voltage dependent entry of Ca++ in nerve endings (Blaustein). Mg++ blocks Ca++ entry and NE depletion from vesicles in situ. Mn++ blocks amine secretion specifically. The excretion of deaminated metabolites is not inhibited. It would appear that the Ca++ serves a similar function in secretion in vivo and in vesicles in situ. Secretion is not mediated by exocytosis. The fusion of vesicle to axollemma is controlled by Na+. Terminals in Ch+-CA++ do not respond to ATP if Na+ is completely omitted from the medium. Lithium inhibits the Na+ dependency.