Adrenergic chromaffin cells are adrenergic even in the absence of epinephrine
Adrenergic chromaffin cells are adrenergic even in the absence of epinephrine
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DOI：
10.1111/jnc.14904
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发表时间：
2019-11-28
影响因子：
4.7
通讯作者：
Borges, Ricardo
中科院分区：
文献类型：
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作者：
Gonzalez-Santana, Ayoze;Castaneyra, Leandro;Borges, Ricardo
肾上腺嗜铬细胞释放肾上腺素（EPI）和去甲肾上腺素（NE）进入血液，作为对压力等情况的稳态反应的一部分。在这里，我们利用EPI缺陷小鼠产生的敲除（KO）的苯乙醇胺N-甲基转移酶（Pnmt）基因。这些Pnmt-KO小鼠被培育成纯合子，但没有表现出主要表型。EPI的缺乏被NE的增加部分补偿，这表明EPI储存在肾上腺素能细胞中被优化。电子显微镜显示，尽管缺乏EPI，嗜铬颗粒保持其形状和一般外观。这表明来自肾上腺素能或去甲肾上腺素能细胞的颗粒即使仅含有NE也保持其特征。急性胰岛素注射大大降低了野生型动物中的EPI含量，NE的降低最小，而Pnmt-KO小鼠中的NE含量仅部分降低。通过电流分析法对胞吐作用的分析显示，相对于野生型颗粒，KO细胞中颗粒的量子尺寸（~ 30%）和I-max（~ 21%）降低，表明NE对肾上腺素能细胞的颗粒基质的亲和力较低。由于电流分析法不能区分肾上腺素能或去甲肾上腺素能细胞，这将表明对基质的亲和力甚至有更大的降低。因此，我们的研究结果表明，肾上腺素能细胞保留其结构特征，尽管几乎完全没有EPI。此外，肾上腺素能细胞的嗜铬颗粒基质被优化以积累EPI，NE是一种较差的替代品。
Adrenal chromaffin cells release epinephrine (EPI) and norepinephrine (NE) into the bloodstream as part of the homeostatic response to situations like stress. Here we utilized EPI-deficient mice generated by knocking out (KO) the phenylethanolamine N-methyltransferase (Pnmt) gene. These Pnmt-KO mice were bred to homozygosis but displayed no major phenotype. The lack of EPI was partially compensated by an increase in NE, suggesting that EPI storage was optimized in adrenergic cells. Electron microscopy showed that despite the lack of EPI, chromaffin granules retain their shape and general appearance. This indicate that granules from adrenergic or noradrenergic cells preserve their characteristics even though they contain only NE. Acute insulin injection largely reduced the EPI content in wild-type animals, with a minimal reduction in NE, whereas there was only a partial reduction in NE content in Pnmt-KO mice. The analysis of exocytosis by amperometry revealed a reduction in the quantum size (-30%) and I-max (-21%) of granules in KO cells relative to the wild-type granules, indicating a lower affinity of NE for the granule matrix of adrenergic cells. As amperometry cannot distinguish between adrenergic or noradrenergic cells, it would suggest even a larger reduction in the affinity for the matrix. Therefore, our results demonstrate that adrenergic cells retain their structural characteristics despite the almost complete absence of EPI. Furthermore, the chromaffin granule matrix from adrenergic cells is optimized to accumulate EPI, with NE being a poor substitute.