IONIC MECHANISMS RELATED TO SECRETION IN PITUITARY CELLS

膜电事件与细胞膜电活动之间的功能耦合， 激素从内分泌细胞的胞吐释放是调节内分泌的关键因素。 内分泌腺分泌的生理学。 的情况下 垂体激素分泌涉及几个膜离子通道 以及耦合刺激和抑制的分子机制 这些离子通道的促分泌受体现在才被发现， 揭示 许多促分泌素受体属于促分泌素超家族， 七种跨膜结构域受体通过鸟嘌呤核苷酸信号传导 结合蛋白（G蛋白）。 在这些受体中， 多巴胺（D2型），催乳素分泌的主要调节剂，和 控制生长激素释放抑制的生长抑素。之间 与这些类型受体偶联的效应物是钾 和钙通道。 近年来，信号的许多元素 将多巴胺受体与这些离子通道连接起来的转导途径 被克隆了。 尤其是钾离子通道， 这些受体是两个跨膜结构域的成员 内向整流钾通道超家族。 我们假设这些- 蛋白偶联钾通道，或GIRKs，是关键的联系， 受体激活和分泌抑制。 原则 本研究的目的是（1）检查分子 特异性的信号通路，其中涉及GIRK，无论是在术语 G蛋白和GIRK通道，（2）严格测试中央 GIRK通道参与分泌调节，和（3） 检查修改的机制和功能作用， 如脱敏。 为此，我们将联合收割机分子 增强和干扰G蛋白和通道的方法 功能与电生理和光学分析的通道和 分泌行为。 所有实验将在 大鼠或小鼠垂体瘤的单个分离垂体细胞 细胞 这项研究将使人们对这些事件有更清楚的了解 垂体细胞中潜在的调节激素分泌。 此外，本发明还提供了一种方法， 脑垂体和垂体中多巴胺受体亚型的共同特性， 大脑以及G蛋白门控K通道的相似性， 组织，表明这些研究可能提供机制的见解， 这些神经递质在情感障碍和神经系统疾病中的作用 调节植物的功能。

The functional coupling between membrane electrical events and exocytotic release of hormones from endocrine cells is a key element in the physiology of secretion in endocrine glands. In the case of pituitary hormone secretion several membrane ion channels are involved and the molecular mechanisms coupling stimulatory and inhibitory secretogogue receptors to these ion channels are only now being revealed. Many secretogogue receptors belong to the superfamily of seven membrane spanning domain receptors signal via guanine nucleotide binding proteins (G-proteins). Among such receptors are those for dopamine (D2 type), the primary regulator of prolactin secretion, and somatostatin which governs inhibition of growth hormone release. Among the effectors to which these classes of receptor couple are potassium and calcium channels. In recent years, many elements of the signal transduction pathways linking dopamine receptors to these ion channels have been cloned. In particular the potassium channels activated by these receptors are members of a two transmembrane spanning domain superfamily of inwardly rectifying K channels. We hypothesize these G- protein coupled K channels, or GIRKs, to be the critical link between receptor activation and the inhibition of secretion. The principle objectives of the present study are to (1) examine the molecular specificity of the signaling pathway which involves GIRK both in terms of G-proteins and GIRK channels, (2) to critically test the central involvment of GIRK channels in the regulation of secretion, and (3) to examine the mechanisms and functional role of modifications to the pathway such as desensitization. To this end we will combine molecular methods to both potentiate and interfere with G-protein and channel function with electrophysiological and optical assays of channel and secretory behavior, respectively. All experiments will be performed in single, isolated pituitary cells of the rat or in mouse pituitary tumor cells. This research will lead to a clearer understanding of the events underlying regulated hormone secretion in pituitary cells. In addition, the common identity of dopamine receptor subtypes in both pituitary and brain as well as similarities in G-protein gated K channels in each tissue, suggest that these studies may provide mechanistic insight into the actions of these neurotransmitters in affective disorders and neural regulation of vegetative functions.