NICOTINIC RECEPTOR STIMULATION ACTIVATES ENKEPHALIN RELEASE AND BIOSYNTHESIS IN ADRENAL CHROMAFFIN CELLS
NICOTINIC RECEPTOR STIMULATION ACTIVATES ENKEPHALIN RELEASE AND BIOSYNTHESIS IN ADRENAL CHROMAFFIN CELLS
复制标题
DOI：
10.1038/312661a0
复制
发表时间：
1984-01-01
期刊：
影响因子：
64.8
通讯作者：
AFFOLTER, HU
中科院分区：
文献类型：
--
作者：
EIDEN, LE;GIRAUD, P;AFFOLTER, HU
当神经内分泌细胞暴露于组织特异性促分泌素时，其释放一部分储存的分泌激素。在肾上腺髓质的情况下，儿茶酚胺和脑啡肽，以及其他分泌蛋白，分泌响应乙酰胆碱，这是释放到嗜铬细胞上的胆碱能受体内脏神经刺激后在vivo 1 -3。促分泌素的刺激消耗细胞内储存的可输出激素。我们有兴趣知道输出激素释放的信号是否也可以通过增强释放激素的生物合成而作为补偿性激素补充的信号。因此，我们研究了烟碱受体刺激对牛嗜铬细胞原代培养物中甲啡肽肽生物合成和脑啡肽原信使RNA表达的影响。我们的研究结果，在这里报告，提出了一个模型的刺激分泌合成耦合，其中烟碱受体占用激活两个途径。一个途径，依赖于钙，而不是模仿增加细胞内的环AMP，导致胞吐激素释放;其他，可能通过钙依赖性增加细胞内的环AMP，导致代偿性增加，通过激活脑啡肽原结构基因的转录细胞内脑啡肽。
Neuroendocrine cells release a portion of their stored secretory hormone content when exposed to tissue-specific secretagogues. In the case of the adrenal medulla, catecholamines and enkephalin peptides, as well as other secretory proteins, are secreted in response to acetylcholine, which is released onto cholinergic receptors on chromaffin cells upon splanchnic nerve stimulationin vivo1–3. Secretagogue stimulation thus depletes intracellular stores of exportable hormone. We were interested to know whether the signal for exportable hormone release might also function as a signal for compensatory hormone repletion by enhancing the biosynthesis of the released hormone(s). Accordingly, we have investigated the effect of nicotinic receptor stimulation on Metenkephalin peptide biosynthesis and expression of proenkephalin messenger RNA in primary cultures of bovine chromaffin cells. Our results, reported here, suggest a model for stimulus–secretion–synthesis coupling in which nicotinic receptor occupancy activates two pathways. One pathway, dependent on calcium and not mimicked by increased intracellular cyclic AMP, leads to exocytotic hormone release; the other, probably via a calcium-dependent increase in intracellular cyclic AMP, leads to a compensatory increase in intracellular enkephalin through activation of transcription of the proenkephalin structural gene.