GABAergic signaling in the rat pineal gland.
GABAergic signaling in the rat pineal gland.
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DOI：
10.1111/jpi.12328
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发表时间：
2016-08
影响因子：
10.3
通讯作者：
Hille B
中科院分区：
文献类型：
--
作者：
Yu H;Benitez SG;Jung SR;Farias Altamirano LE;Kruse M;Seo JB;Koh DS;Muñoz EM;Hille B
松果体细胞在夜间分泌褪黑激素，以响应松果体中交感神经末梢释放的去甲肾上腺素。松果体还含有许多其他神经递质，其细胞分布、活动以及与松果体功能的相关性尚不清楚。在这里，我们澄清来源，并证明神经递质γ-氨基丁酸（GABA）的细胞作用，使用免疫印迹和免疫组织化学的腺体和松果体细胞的电记录。GABA能细胞和神经纤维，定义为含有GABA和合成酶GAD 67，进行了鉴定。这些细胞代表间质细胞的一个子集，而神经纤维与交感神经支配不同。GABAA受体亚单位α1在GABA能和交感神经纤维附近以及松果体细胞和血管之间的细微延伸处可见。GABAB 1受体亚单位定位于间质室，但不是在松果体细胞。离体松果体细胞的电生理学显示，GABA和蝇蕈醇引起强烈的内向氯电流荷包牡丹碱和印防己毒素敏感，明确的证据功能GABAA受体的表面膜上。应用高钾溶液或神经递质乙酰胆碱使松果体细胞膜电位去极化，足以打开电压门控Ca 2+通道，导致细胞内钙升高。γ-氨基丁酸使细胞膜重新极化，阻止了钙离子的上升。在48-72小时培养的完整腺体，GABA的应用既不触发褪黑激素分泌本身也不影响去甲肾上腺素诱导的分泌。因此，强烈的GABA信号元件存在于松果体中，使松果体细胞产生大的电反应，但生理作用需要被发现。
Pinealocytes secrete melatonin at night in response to norepinephrine released from sympathetic nerve terminals in the pineal gland. The gland also contains many other neurotransmitters whose cellular disposition, activity, and relevance to pineal function are not understood. Here we clarify sources and demonstrate cellular actions of the neurotransmitter γ-aminobutyric acid (GABA) using Western blotting and immunohistochemistry of the gland and electrical recording from pinealocytes. GABAergic cells and nerve fibers, defined as containing GABA and the synthetic enzyme GAD67, were identified. The cells represent a subset of interstitial cells while the nerve fibers were distinct from the sympathetic innervation. The GABAA receptor subunit α1 was visualized in close proximity of both GABAergic and sympathetic nerve fibers as well as fine extensions among pinealocytes and blood vessels. The GABAB1 receptor subunit was localized in the interstitial compartment but not in pinealocytes. Electrophysiology of isolated pinealocytes revealed that GABA and muscimol elicit strong inward chloride currents sensitive to bicuculline and picrotoxin, clear evidence for functional GABAA receptors on the surface membrane. Applications of elevated potassium solution or the neurotransmitter acetylcholine depolarized the pinealocyte membrane potential enough to open voltage-gated Ca2+ channels leading to intracellular calcium elevations. GABA repolarized the membrane and shut off such calcium rises. In 48–72-h cultured intact glands, GABA application neither triggered melatonin secretion by itself nor affected norepinephrine-induced secretion. Thus strong elements of GABA signaling are present in pineal glands that make large electrical responses in pinealocytes, but physiological roles need to be found.