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基于与电化学质子梯度偶联的嗜铬粒蛋白颗粒和空泡中生物胺积累模型。

A model of biogenic amine accumulation into chromaffin granules and ghosts based on coupling to the electrochemical proton gradient.

作者信息

Johnson R G, Carty S, Scarpa A

出版信息

Fed Proc. 1982 Sep;41(11):2746-54.

PMID:7117549
Abstract

A model is presented to explain catecholamine uptake into isolated chromaffin granules and ghosts. It is based on the following observations and conclusions: 1) the chromaffin granule maintains one of the lowest permeabilities to cations of any previously isolated subcellular organelle and the lowest permeability to protons, 2) a transmembrane proton gradient delta pH exists across the chromaffin granule membrane that is not media dependent, with a measured internal pH of 5.5; 3) the addition of ATP to a suspension of chromaffin granules results in the generation of a membrane potential of 80-100 mV, positive inside; 4) an H+-translocating ATPase responsible for the generation of this electrochemical proton gradient (delta micro H+) exists within the membrane of the chromaffin granule; 5) net amine accumulation proceeds in the presence of both a delta pH alone and a transmembrane potential gradient delta psi alone, with the maximal rate and extent occurring in the presence of a delta pH and a delta psi together (delta micro H+); 6) when catecholamine uptake is in equilibrium with the delta micro H+, the equilibrium distribution of amines (delta micro A) obeys the relationship delta micro A = delta psi-2Zdelta pH. The model, in its elemental form, states that an H+-translocating ATPase for the generation of a delta pH and delta psi exists within the membrane of the chromaffin granule. This electrochemical proton gradient provides the driving force for amine influx, which proceeds via a reserpine-sensitive antiport carrier mechanism coupled to proton efflux. The model is discussed in terms of its physiological implications and significance for other amine-containing subcellular organelles, with particular respect to the species of catecholamine transported, and other unresolved issues.

摘要

本文提出了一个模型来解释儿茶酚胺摄取到分离的嗜铬颗粒和空泡中的机制。该模型基于以下观察结果和结论:1)嗜铬颗粒对阳离子的通透性是所有先前分离的亚细胞器中最低的之一,对质子的通透性最低;2)跨嗜铬颗粒膜存在一个跨膜质子梯度ΔpH,它不依赖于介质,测得的内部pH为5.5;3)向嗜铬颗粒悬浮液中添加ATP会导致产生80-100 mV的膜电位,内部为正;4)嗜铬颗粒膜内存在一种负责产生这种电化学质子梯度(ΔμH⁺)的H⁺转运ATP酶;5)仅在单独的ΔpH或单独的跨膜电位梯度Δψ存在时,净胺积累就会发生,而在ΔpH和Δψ同时存在(ΔμH⁺)时,积累速率和程度最大;6)当儿茶酚胺摄取与ΔμH⁺达到平衡时,胺的平衡分布(ΔμA)遵循关系ΔμA = Δψ - 2ZΔpH。该模型的基本形式表明,嗜铬颗粒膜内存在一种用于产生ΔpH和Δψ的H⁺转运ATP酶。这种电化学质子梯度为胺的流入提供驱动力,胺的流入通过与质子外流偶联的利血平敏感的反向转运载体机制进行。本文从其生理意义以及对其他含胺亚细胞器的重要性方面对该模型进行了讨论,特别涉及所运输的儿茶酚胺种类以及其他未解决的问题。

相似文献

1
A model of biogenic amine accumulation into chromaffin granules and ghosts based on coupling to the electrochemical proton gradient.基于与电化学质子梯度偶联的嗜铬粒蛋白颗粒和空泡中生物胺积累模型。
Fed Proc. 1982 Sep;41(11):2746-54.
2
Mechanisms of proton-linked monoamine transport in chromaffin granule ghosts.嗜铬粒蛋白颗粒膜泡中质子偶联单胺转运的机制
Fed Proc. 1982 Sep;41(11):2742-5.
3
Mechanisms of accumulation of tyramine, metaraminol, and isoproterenol in isolated chromaffin granules and ghosts.酪胺、间羟胺和异丙肾上腺素在分离的嗜铬粒和空泡中的蓄积机制。
Biochem Pharmacol. 1982 Mar 1;31(5):815-23. doi: 10.1016/0006-2952(82)90468-3.
4
Adenosine triphosphate in the bovine chromaffin granule.牛嗜铬颗粒中的三磷酸腺苷
J Physiol (Paris). 1978;74(5):503-8.
5
Proton: substrate stoichiometries during active transport of biogenic amines in chromaffin ghosts.质子:嗜铬细胞空泡中生物胺主动转运过程中的底物化学计量学
J Biol Chem. 1981 Jun 10;256(11):5773-80.
6
Biological amine transport in chromaffin ghosts. Coupling to the transmembrane proton and potential gradients.嗜铬细胞空泡中的生物胺转运。与跨膜质子和电位梯度的偶联。
J Biol Chem. 1979 Nov 10;254(21):10963-72.
7
Protonmotive force and catecholamine transport in isolated chromaffin granules.分离的嗜铬颗粒中的质子动力和儿茶酚胺转运
J Biol Chem. 1979 May 25;254(10):3750-60.
8
Anion and proton transport in chromaffin granules.嗜铬颗粒中的阴离子与质子转运
Fed Proc. 1982 Sep;41(11):2769-74.
9
Spectrophotometric measurements of transmembrane potential and pH gradients in chromaffin granules.嗜铬颗粒中跨膜电位和pH梯度的分光光度测量。
J Gen Physiol. 1980 Feb;75(2):109-40. doi: 10.1085/jgp.75.2.109.
10
Both the transmembrane pH gradient and the membrane potential are important in the accumulation of amines by resealed chromaffin-granule 'ghosts'.跨膜pH梯度和膜电位在重封的嗜铬粒蛋白颗粒“空壳”积累胺类物质的过程中都很重要。
FEBS Lett. 1980 Mar 10;111(2):386-90. doi: 10.1016/0014-5793(80)80833-7.

引用本文的文献

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Molecular requirements of chromogranin B for the long-sought anion shunter of regulated secretion.嗜铬粒蛋白B对长期寻找的调节性分泌阴离子分流器的分子要求。
Int J Biol Macromol. 2025 May;309(Pt 1):142180. doi: 10.1016/j.ijbiomac.2025.142180. Epub 2025 Mar 17.
2
Chromogranin B (CHGB) is dimorphic and responsible for dominant anion channels delivered to cell surface via regulated secretion.嗜铬粒蛋白B(CHGB)具有双态性,负责通过调节性分泌传递到细胞表面的主要阴离子通道。
Front Mol Neurosci. 2023 Jun 26;16:1205516. doi: 10.3389/fnmol.2023.1205516. eCollection 2023.
3
Secretory granule protein chromogranin B (CHGB) forms an anion channel in membranes.
分泌颗粒蛋白嗜铬粒蛋白B(CHGB)在细胞膜中形成阴离子通道。
Life Sci Alliance. 2018 Sep 24;1(5):e201800139. doi: 10.26508/lsa.201800139. eCollection 2018 Oct.
4
Na(+)/H(+) exchanger inhibition modifies dopamine neurotransmission during normal and metabolic stress conditions.钠/氢交换体抑制在正常和代谢应激条件下会改变多巴胺神经传递。
J Neurochem. 2008 Jul;106(1):231-43. doi: 10.1111/j.1471-4159.2008.05355.x. Epub 2008 Jul 1.
5
Effects of lowering extracellular and cytosolic pH on calcium fluxes, cytosolic calcium levels, and transmitter release in presynaptic nerve terminals isolated from rat brain.降低细胞外和细胞内pH值对从大鼠脑部分离出的突触前神经末梢中钙通量、细胞内钙水平及递质释放的影响。
J Gen Physiol. 1988 Feb;91(2):305-15. doi: 10.1085/jgp.91.2.305.
6
Cystine transport in purified rat liver lysosomes.纯化大鼠肝脏溶酶体中的胱氨酸转运
Biochem J. 1986 Jun 15;236(3):671-7. doi: 10.1042/bj2360671.
7
Thyrotropin induces the acidification of the secretory granules of parafollicular cells by increasing the chloride conductance of the granular membrane.促甲状腺激素通过增加颗粒膜的氯电导来诱导甲状腺滤泡旁细胞分泌颗粒的酸化。
J Cell Biol. 1988 Dec;107(6 Pt 1):2137-47. doi: 10.1083/jcb.107.6.2137.