Effects of reserpine and tetrabenazine on catecholamine and ATP storage in cultured bovine adrenal medullary chromaffin cells.
Effects of reserpine and tetrabenazine on catecholamine and ATP storage in cultured bovine adrenal medullary chromaffin cells.
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利血平和丁苯那嗪对培养的牛肾上腺髓质嗜铬细胞中儿茶酚胺和 ATP 储存的影响。
DOI：
10.1111/j.1471-4159.1987.tb02901.x
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发表时间：
1987
影响因子：
4.7
通讯作者：
Kirshner,N
中科院分区：
文献类型：
--
作者：
Caughey,B;Kirshner,N
使用阻断囊泡儿茶酚胺摄取的药物研究了培养的牛肾上腺髓质细胞的嗜铬囊泡中儿茶酚胺和 ATP 之间的体内储存关系。三天的利血平和丁苯那嗪治疗导致儿茶酚胺消耗 85-90%，导致细胞 ATP 含量减少 41-46%。利血平处理细胞的亚细胞分级表明 ATP 从嗜铬囊泡池中丢失。这在使用代谢抑制剂区分囊泡和囊外 ATP 库的实验中得到了证实。囊泡 ATP 损失与儿茶酚胺的损失不成正比，导致处理 48 h 后，嗜铬囊泡中儿茶酚胺与 ATP 的摩尔比降低了 50%。在代谢标记研究中，发现利血平治疗选择性地减少[3H]腺苷掺入囊泡ATP，但同时减少了32Pi掺入囊泡和囊外池。 [3H]腺苷掺入的减少并不是由于低儿茶酚胺水平导致的囊泡核苷酸摄取减少所致，因为当丁苯那嗪预处理耗尽儿茶酚胺并在标记前除去药物时，没有观察到[3H]腺苷掺入的减少。当在标记过程中存在时，丁苯那嗪被发现是质膜腺苷摄取的可逆抑制剂。体内儿茶酚胺耗尽的嗜铬小泡中观察到的腺嘌呤核苷酸损失提供了证据，证明 ATP 和儿茶酚胺之间的相互作用对于高浓度这些化合物的囊泡储存非常重要。
The in vivo storage relationship between catechol‐amines and ATP in chromaffin vesicles of cultured bovine adrenal medulla cells was investigated using drugs that block vesicular catecholamine uptake. Three‐day treatments with reserpine and tetrabenazine causing 85–90% depletion of catecholamines resulted in 41–46% reductions in cellular ATP content. Subcellular fractionation of reserpine‐treated cells indicated that the ATP is lost from the chromaffin vesicle pool. This was confirmed in experiments using metabolic inhibitors to differentiate the vesicular and extravesicular ATP pools. The vesicular ATP loss was not proportional to that of catecholamines, resulting in a reduction by 50% in the chromaffin vesicle mole ratio of catecholamines to ATP after 48 h of treatment. In metabolic labeling studies, it was found that reserpine treatment reduced the incorporation of [3H]adenosine into vesicular ATP selectively, but it reduced the incorporation of32Piinto both the vesicular and extravesicular pools. The reduction of the [3H]adenosine incorporation was not due to diminished vesicular nucleotide uptake resulting from low catecholamine levels, because when the catecholamines were depleted by tetrabenazine pretreatment followed by removal of the drug before labeling, no reduction in [3H]adenosine incorporation was observed. When present during the labeling, tetrabenazine was found to be a reversible inhibitor of plasma membrane adenosine uptake. The observed loss of adenine nucleotides from catecholamine‐depleted chromaffin vesicles in vivo provides evidence that interactions between ATP and catecholamines are important in the vesicular storage of high concentrations of these compounds.