PACAP and acetylcholine cause distinct Ca2+ signals and secretory responses in chromaffin cells.
PACAP and acetylcholine cause distinct Ca2+ signals and secretory responses in chromaffin cells.
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DOI：
10.1085/jgp.202213180
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发表时间：
2023-02-06
影响因子：
3.8
通讯作者：
Anantharam, Arun
中科院分区：
文献类型：
--
作者：
Morales, Alina;Mohan, Ramkumar;Chen, Xiaohuan;Coffman, Breanna L.;Bendahmane, Mounir;Watch, Lester;West, Joshua L.;Bakshi, Shreeya;Traynor, John R.;Giovannucci, David R.;Kammermeier, Paul J.;Axelrod, Daniel;Currie, Kevin P. M.;Smrcka, Alan V.;Anantharam, Arun
PACAP是内脏-嗜铬细胞突触的重要神经递质，但其刺激分泌的机制尚不清楚。在这里，我们表明，PACAP通过涉及Gαs，PLCε和L-型钙通道的途径发挥作用。肾上腺髓质嗜铬细胞将化学信息转换成输出，调节整个外周的终末器官功能。至少有两种重要的神经递质是通过支配节前神经元来释放的，以刺激嗜铬细胞中的胞吐作用-乙酰胆碱（ACh）和垂体腺苷酸环化酶激活多肽（PACAP）。虽然PACAP被广泛认为是一个重要的促分泌素在这个系统中，耦合PACAP刺激嗜铬细胞分泌的途径知之甚少。本研究的目的是解决这一知识差距。在这里，它表明，PACAP激活Gα s-偶联途径，必须通过磷脂酶C ε（PLCε）的信号，以驱动Ca 2+内流和胞吐。PACAP刺激导致嗜铬细胞中的Ca 2+信号的复杂模式，导致持续的分泌反应，其在动力学上不同于ACh刺激的形式。由PACAP引起的胞吐作用与比ACh刺激的胞吐作用更慢的肽货物释放有关。重要的是，在缺乏PLCε表达的细胞中，只有对PACAP的分泌反应而不是ACh被消除。数据显示，ACh和PACAP，通过不同的信号通路，使细微差别和可变的分泌输出嗜铬细胞。
PACAP is an important neurotransmitter at the splanchnic-chromaffin cell synapse, but the mechanisms by which it stimulates secretion are poorly understood. Here we show that PACAP operates through a pathway that involves Gαs, PLCε, and L-type calcium channels. The adrenomedullary chromaffin cell transduces chemical messages into outputs that regulate end organ function throughout the periphery. At least two important neurotransmitters are released by innervating preganglionic neurons to stimulate exocytosis in the chromaffin cell—acetylcholine (ACh) and pituitary adenylate cyclase activating polypeptide (PACAP). Although PACAP is widely acknowledged as an important secretagogue in this system, the pathway coupling PACAP stimulation to chromaffin cell secretion is poorly understood. The goal of this study is to address this knowledge gap. Here, it is shown that PACAP activates a Gαs-coupled pathway that must signal through phospholipase C ε (PLCε) to drive Ca2+ entry and exocytosis. PACAP stimulation causes a complex pattern of Ca2+ signals in chromaffin cells, leading to a sustained secretory response that is kinetically distinct from the form stimulated by ACh. Exocytosis caused by PACAP is associated with slower release of peptide cargo than exocytosis stimulated by ACh. Importantly, only the secretory response to PACAP, not ACh, is eliminated in cells lacking PLCε expression. The data show that ACh and PACAP, acting through distinct signaling pathways, enable nuanced and variable secretory outputs from chromaffin cells.
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DOI：
10.1007/s00424-017-2062-3
发表时间：
2018-01
期刊：
Pflugers Archiv : European journal of physiology
影响因子：
--
作者：
Eiden LE;Emery AC;Zhang L;Smith CB
通讯作者：
Smith CB
影响因子：
7.3
作者：
DOUGLAS, WW
通讯作者：
DOUGLAS, WW
影响因子：
3.3
作者：
CHOWDHURY, PS;GUO, X;WAKADE, AR
通讯作者：
WAKADE, AR
刺激神经神经后，肾上腺髓质中神经末端的亚显微镜变化。
DOI：
10.1083/jcb.3.4.611
发表时间：
1957-07-25
期刊：
The Journal of biophysical and biochemical cytology
影响因子：
--
作者：
DE ROBERTIS, E;FERREIRA, A V
通讯作者：
FERREIRA, A V
影响因子：
5.3
作者：
Calejo, Ana Isabel;Jorgacevski, Jernej;Zorec, Robert
通讯作者：
Zorec, Robert