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）的摄取和保留 在肾上腺素能神经轴浆（原位）的突触囊泡中 终端在体外。当大鼠心室切片在 Na+剥夺（12.5至25 μ M Na，胆碱）Krebs-碳酸氢盐培养基 (Ch+-Ca++），突触囊泡和轴膜似乎建立了一个新的 能分泌NE并能在脑内重新捕获NE的形态单位 介质这个实验室是最早认识到电子 运输可能与滞留有关。分泌是由 胺泵在轴膜和夺回是介导的胺泵在 囊泡膜。在这种准备中，后者取决于 外源性ATP Mg ~（++）-ATP酶抑制滞留和再捕获 抑制剂，K+-H+交换离子载体，H+离子载体和利血平， 阻断囊泡膜中的NE泵。这些抑制剂都是已知的 阻断依赖于H+转运的吸收， 囊泡膜上的Mg ~（++）-ATP酶。此外，吸收和保留是 防止氨。得出的结论是， 囊泡在原位由pH梯度，Δ pH，跨越 囊泡膜（Bogdanski，1982，1983，1986，1988）。 这些发现具有生理学意义。同样的抑制剂可以防止 NE在KRB孵育终末的滞留。Mg++和Mn++阻断了 神经末梢中Ca++的电压依赖性进入（Blaustein）。Mg++块 Ca++内流和NE从囊泡原位耗竭。Mn++阻断胺 具体来说就是分泌。脱氨基代谢物的排泄不是 压抑似乎Ca++在细胞中起着类似的作用。 在体内和囊泡原位分泌。分泌不是由 胞吐作用 囊泡与轴膜的融合受Na+控制。终端 如果Na+完全不存在，Ch+-CA++对ATP无反应。 介质锂抑制Na+依赖性。

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.