Differential quantal release of histamine and 5-hydroxytryptamine from mast cells of vesicular monoamine transporter 2 knockout mise

Differential quantal release of histamine and 5-hydroxytryptamine from mast cells of vesicular monoamine transporter 2 knockout mise
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DOI:
10.1073/pnas.97.1.162
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发表时间:
2000-01-04
影响因子:
11.1
通讯作者:
Wightman, RM
Wightman, RM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Travis, ER;Wang, YM;Wightman, RM

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最近可用的小鼠缺乏神经元形式的囊泡单胺转运蛋白2(VMAT 2)提供了机会,研究其在存储和释放的作用。碳纤维微电极被用来测量组胺和5-羟色胺(5-HT)从VMAT 2表达肥大细胞作为量子释放的模型系统的单个分泌事件。VMAT 2对于单胺储存是必不可少的,因为来自纯合(VMAT 2(-/-))小鼠的肥大细胞在经历颗粒细胞融合时不释放单胺。来自杂合动物(VMAT 2(+/-))的细胞比来自野生型对照的细胞分泌更低量的单胺/颗粒。对VMAT 2(+/-)细胞中组胺和5-HT从颗粒中共同释放的研究表明,5-HT的量子尺寸比组胺减少得更多。因此,虽然囊泡运输是决定5-HT和组胺释放的量子大小的限制因素,但与肝素基质的颗粒内缔合也起着重要作用。
The recent availability of mice lacking the neuronal form of the vesicular monoamine transporter 2 (VMAT2) affords the opportunity to study its roles in storage and release. Carbon fiber microelectrodes were used to measure individual secretory events of histamine and 5-hydroxytryptamine (5-HT) from VMAT2-expressing mast cells as a model system for quantal release. VMAT2 is indispensable for monoamine storage because mast cells from homozygous (VMAT2(-/-)) mice, while undergoing granule-cell fusion, do not release monoamines, Cells from heterozygous animals (VMAT2(+/-)) secrete lower amounts of monoamine per granule than cells from wild-type controls. Investigation of corelease of histamine and 5-HT from granules in VMAT2(+/-) cells revealed 5-HT quantal size was reduced more than that of histamine. Thus, although vesicular transport is the limiting factor determining quantal size of 5-HT and histamine release, intragranular association with the heparin matrix also plays a significant role.