电压敏感性钙通道在垂体激素释放中的作用。

Participation of voltage-sensitive calcium channels in pituitary hormone release.

作者信息

Stojilković S S, Izumi S, Catt K J

机构信息

Endocrinology and Reproductive Research Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.

出版信息

J Biol Chem. 1988 Sep 15;263(26):13054-61.

PMID:2458342

Abstract

The role of extracellular Ca2+ in pituitary hormone release was studied in primary cultures of rat anterior pituitary cells. The basal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin (TSH), and adrenocorticotropin (ACTH) secretion were independent of extracellular Ca2+ concentration ([Ca2+]e). In contrast, the basal levels of growth hormone (GH) and prolactin (PRL) release showed dose-dependent increases with elevation of [Ca2+]e, and were abolished by Ca2+-channel antagonists. Under Ca2+-deficient conditions, BaCl2 mimicked the effects of calcium on PRL and GH release but with a marked increase in potency, and also increased basal LH and FSH release in a dose-dependent manner. In the presence of normal [Ca2+]e, depolarization with K+ maximally increased cytosolic [Ca2+] ([Ca2+]i) from 100 to 185 nM and elevated LH, FSH, TSH, ACTH, PRL, and GH release by 7-, 5-, 4-, 3-, 2-, and 1.5-fold, respectively. These effects of KCl were abolished in Ca2+-deficient medium or in the presence of the Ca2+-channel antagonist, Co2+, and were diminished by the dihydropyridine Ca2+-channel antagonist, nifedipine. The Ca2+-channel agonist BK 8644 (100 nM) enhanced the hormone-releasing actions of 25 mM KCl upon PRL, LH, FSH, GH, TSH, and ACTH by 2.3-, 2.0-, 1.8-, 1.7-, 1.6-, and 1.4-fold, respectively. The dose- and voltage-dependent actions of BK 8644 were specific for individual cell types; BK 8644 enhanced GH, PRL, TSH, LH, and ACTH secretion in the absence of any depolarizing stimulus, with ED50 values of 8, 10, 150, 200, and 400 nM, respectively. However, in the presence of 50 mM KCl, the ED50 values for BK 8644 were 1.5, 2, 3, 5, and 7 nM for GH, PRL, ACTH, TSH, and LH, respectively. [3H]BK 8644 bound specifically to pituitary membranes with Kd values of 0.8 nM and concentrations of about 900 channels per cell. These observations provide evidence for the presence and participation of voltage-sensitive calcium channels in the secretion of all five populations of anterior pituitary cells.

摘要

在大鼠垂体前叶细胞的原代培养物中研究了细胞外Ca2+在垂体激素释放中的作用。促黄体生成素（LH）、促卵泡激素（FSH）、促甲状腺激素（TSH）和促肾上腺皮质激素（ACTH）的基础分泌水平与细胞外Ca2+浓度（[Ca2+]e）无关。相反，生长激素（GH）和催乳素（PRL）释放的基础水平随着[Ca2+]e的升高呈剂量依赖性增加，并且被Ca2+通道拮抗剂所消除。在Ca2+缺乏的条件下，BaCl2模拟了钙对PRL和GH释放的作用，但效力显著增加，并且也以剂量依赖性方式增加了基础LH和FSH的释放。在正常[Ca2+]e存在的情况下，用K+进行去极化使胞质Ca2+（[Ca2+]i）从100 nM最大增加到185 nM，并使LH、FSH、TSH、ACTH、PRL和GH的释放分别增加7倍、5倍、4倍、3倍、2倍和1.5倍。KCl的这些作用在Ca2+缺乏的培养基中或在Ca2+通道拮抗剂Co2+存在时被消除，并且被二氢吡啶Ca2+通道拮抗剂硝苯地平减弱。Ca2+通道激动剂BK 8644（100 nM）使25 mM KCl对PRL、LH、FSH、GH、TSH和ACTH释放的激素释放作用分别增强2.3倍、2.0倍、1.8倍、1.7倍、1.6倍和1.4倍。BK 8644的剂量和电压依赖性作用对单个细胞类型具有特异性；BK 8644在没有任何去极化刺激的情况下增强了GH、PRL、TSH、LH和ACTH的分泌，其半数有效剂量（ED50）值分别为8 nM、10 nM、150 nM、200 nM和400 nM。然而，在50 mM KCl存在的情况下，BK 8644对GH、PRL、ACTH、TSH和LH的ED50值分别为1.5 nM、2 nM、3 nM、5 nM和7 nM。[3H]BK 8644特异性结合到垂体膜上，解离常数（Kd）值为0.8 nM，每个细胞约有900个通道。这些观察结果为电压敏感性钙通道在垂体前叶所有五种细胞群体的分泌中的存在和参与提供了证据。