Reetz A, Solimena M, Matteoli M, Folli F, Takei K, De Camilli P
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510.
EMBO J. 1991 May;10(5):1275-84. doi: 10.1002/j.1460-2075.1991.tb08069.x.
GABA, a major inhibitory neurotransmitter of the brain, is also present at high concentration in pancreatic islets. Current evidence suggests that within islets GABA is secreted from beta-cells and regulates the function of mantle cells (alpha- and delta-cells). In the nervous system GABA is stored in, and secreted from, synaptic vesicles. The mechanism of GABA secretion from beta-cells remains to be elucidated. Recently the existence of synaptic-like microvesicles has been demonstrated in some peptide-secreting endocrine cells. The function of these vesicles is so far unknown. The proposed paracrine action of GABA in pancreatic islets makes beta-cells a useful model system to explore the possibility that synaptic-like microvesicles, like synaptic vesicles, are involved in the storage and release of non-peptide neurotransmitters. We report here the presence of synaptic-like microvesicles in beta-cells and in beta-cells. Some beta-cells in culture were found to extend neurite-like processes. When these were present, synaptic-like microvesicles were particularly concentrated in their distal portions. The GABA synthesizing enzyme, glutamic acid decarboxylase (GAD), was found to be localized around synaptic-like microvesicles. This was similar to the localization of GAD around synaptic vesicles in GABA-secreting neurons. GABA immunoreactivity was found to be concentrated in regions of beta-cells which were enriched in synaptic-like microvesicles. These findings suggest that in beta-cells synaptic-like microvesicles are storage organelles for GABA and support the hypothesis that storage of non-peptide signal molecules destined for secretion might be a general feature of synaptic-like microvesicles of endocrine cells.
γ-氨基丁酸（GABA）是大脑中的一种主要抑制性神经递质，在胰岛中也以高浓度存在。目前的证据表明，在胰岛内，GABA由β细胞分泌，并调节被膜细胞（α细胞和δ细胞）的功能。在神经系统中，GABA存储于突触小泡并从突触小泡中分泌。β细胞分泌GABA的机制仍有待阐明。最近，在一些分泌肽的内分泌细胞中已证实存在类似突触的微泡。这些微泡的功能目前尚不清楚。GABA在胰岛中拟有的旁分泌作用使β细胞成为一个有用的模型系统，以探索类似突触的微泡是否像突触小泡一样参与非肽神经递质的存储和释放。我们在此报告在β细胞中存在类似突触的微泡。在培养的一些β细胞中发现有类似神经突的突起。当这些突起存在时，类似突触的微泡特别集中在其远端部分。发现γ-氨基丁酸合成酶，即谷氨酸脱羧酶（GAD），定位于类似突触的微泡周围。这与GAD在分泌GABA的神经元中突触小泡周围的定位相似。发现GABA免疫反应性集中在富含类似突触微泡的β细胞区域。这些发现表明，在β细胞中，类似突触的微泡是GABA的存储细胞器，并支持这样一种假说，即 destined for secretion 的非肽信号分子的存储可能是内分泌细胞类似突触微泡的一个普遍特征。 （注：原文中“destined for secretion”表述不太准确，可能影响理解，大致意思是“用于分泌的”。）
