Eiden L E, Giraud P, Dave J R, Hotchkiss A J, Affolter H U
Nature. 1984;312(5995):661-3. doi: 10.1038/312661a0.
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 stimulation in vivo. 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 Met-enkephalin 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.
神经内分泌细胞在暴露于组织特异性促分泌素时，会释放其储存的部分分泌激素。就肾上腺髓质而言，儿茶酚胺、脑啡肽以及其他分泌蛋白会在乙酰胆碱的作用下分泌，乙酰胆碱在体内内脏神经刺激时释放到嗜铬细胞的胆碱能受体上。因此，促分泌素刺激会耗尽细胞内可输出激素的储存。我们想知道可输出激素释放的信号是否也可能通过增强所释放激素的生物合成，而作为补偿性激素补充的信号。相应地，我们研究了烟碱受体刺激对原代培养的牛嗜铬细胞中甲硫氨酸脑啡肽生物合成及前脑啡肽信使核糖核酸表达的影响。我们在此报告的结果提示了一种刺激-分泌-合成偶联模型，其中烟碱受体占据激活两条途径。一条途径依赖于钙，且不受细胞内环磷酸腺苷增加的模拟，导致激素通过胞吐作用释放；另一条途径可能通过细胞内环磷酸腺苷的钙依赖性增加，通过激活前脑啡肽结构基因的转录导致细胞内脑啡肽的补偿性增加。
