INTRACELLULAR SIGNALING IN ENDOCRINE CELLS

电压敏感性和电压不敏感性钙离子内流的整合 促性腺激素释放激素（GnRH）诱导的钙通道 动员和黄体生成素（LH）释放进行了研究， 垂体前叶促性腺激素细胞 增加钙进入 制霉菌素穿孔细胞中的电压敏感性钙通道， 与两种不同的促性腺激素释放激素诱发的钙的积极作用有关 release. 它有助于减少尖峰间期， 来增加峰值的频率， 通过增加钙离子的持续时间和幅度来进行信号传导 振荡 在细胞中观察到同样的效果， 振荡由InsP 3诱导。 垂体促性腺激素细胞也表达 ATP门控受体通道。 它们的激活引起钙内流， 细胞溶质钙浓度随之增加。嘌呤能 通道是电压不敏感的，但它们的激活与 促性腺激素细胞的去极化和额外的促进 钙通过电压敏感钙通道进入。 嘌呤能 通道介导的钙内流也影响激动剂诱导的和 InsP 3依赖性钙振荡通过增加频率， 基线和峰值持续时间。 电压敏感和 ATP门控钙通道对钙峰频率的影响 与钙尖峰的模型模拟一致，其中小的 细胞质钙浓度的增加能够触发大的 在存在恒定InsP 3的情况下的钙振荡脉冲 浓度. 这两种钙离子进入途径也能增强GnRH诱导的 LH释放 促性腺激素细胞被发现与LH共分泌ATP， 表明嘌呤能表达的生理意义 这些细胞中的通道。 在灌注的垂体细胞中，ATP迅速地 被胞外ATP酶、胞外腺苷酸酶和胞外5'核苷酸酶降解， 腺苷以钙/镁依赖的方式。 这些观察结果 表明ATP代表正反馈元素， 激动剂诱导的钙信号传导和促性腺激素分泌， 该作用由外核苷酸酶控制。

The integration of voltage-sensitive and -insensitive calcium entry pathways in gonadotropin-releasing hormone (GnRH)-induced calcium mobilization and luteinizing hormone (LH) release were investigated in anterior pituitary gonadotrophs. Increase in calcium entry through voltage-sensitive calcium channels in nystatin-perforated cells is associated with two distinct positive effects on GnRH-evoked calcium release. It facilitates a decrease in the interspike periods that lead to increase in the frequency of spiking and also magnifies calcium signaling by increasing the duration and amplitude of calcium oscillations. The same effects are observed in cells in which calcium oscillations are induced by InsP3. Pituitary gonadotrophs also express ATP-gated receptor channels. Their activation causes calcium influx and a consequent increase in cytosolic calcium concentrations. Purinergic channels are voltage-insensitive, but their activation is associated with the depolarization of gonadotrophs and the additional facilitation of calcium entry through voltage-sensitive calcium channels. Purinergic channel-mediated calcium influx also affects agonist-induced and InsP3-dependent calcium oscillations by increasing the frequency, baseline, and duration of spiking. The effects of voltage-sensitive and ATP-gated calcium channels on the frequency of calcium spiking are consistent with the model simulation of calcium spiking, in which a small increase in cytosolic calcium concentrations is able to trigger a large pulse of calcium oscillations in the presence of a constant InsP3 concentration. Both calcium entry pathways also potentiate GnRH-induced LH release. Gonadotrophs were found to co-secrete ATP with LH, indicating the physiological significance of the expression of purinergic channels in these cells. In perifused pituitary cells, ATP is promptly degraded by ecto-ATPase, ecto-ADPase, and ecto-5' nucleotidase to adenosine in a calcium/magnesium-dependent manner. These observations indicate that ATP represents a positive feedback element in agonist-induced calcium signaling and gonadotropin secretion, and that this action is controlled by ectonucleotidases.