NEUROPEPTIDE AND TRANSMITTER ACTION IN SECRETORY CELLS

拟议的研究旨在了解分子事件。 参与细胞功能的抑制性调节因子的作用 与靶细胞受体的初始相互作用到最终的生物 分泌物减少的反应。本研究的主要目标是 计划是研究神经肽生长抑素的机制 在不同的靶细胞中诱导其作用。建议的研究将 关注生长抑素在两个克隆细胞系中的作用：和 脑垂体前叶来源的内分泌细胞系 神经母细胞瘤来源的细胞株。这些细胞保留了许多 起源组织的不同功能，并具有几个独特的 容易允许研究的属性将是困难的或 在其他系统中无法解释。此外，初步研究 表明这两种细胞系中的生长抑素受体是 不一样。我们将研究生长抑素作用的以下几个方面： 1.生长抑素调节细胞内游离钙的机制 胞浆游离浓度及其诱导变化的重要性 CA2在介导生长抑素抑制分泌中的作用 2.对细胞结合和转导特性的调节 生长抑素受体。 3.生长抑素作用终止的机制。 4.结合性质、配体处理能力和 内分泌和神经靶细胞中生长抑素受体的结构。 这项研究计划的一个次要目标是检查对 脑下垂体功能由神经递质腺苷实现。因此， 腺苷受体激动剂和拮抗剂对垂体激素的影响 分泌物将在原代培养中确定。此外， 参与腺苷作用的细胞内介质将在 克隆性垂体细胞系。

The proposed studies are aimed at understanding the molecular events involved in the action of inhibitory regulators of cell function from their initial interaction with target cell receptors to the final biological response of reduced secretion. The major objective of the present research plan is to investigate the mechanism by which the neuropeptide somatostatin elicits its effects in different target cells. The studies proposed will focus on the actions of somatostatin in two clonal cell lines: and endocrine cell line derived from th anterior pituitary and a neuroblastoma-derived cell strain. These cells have retained many of the differentiated functions of the tissue of origin and possess several unique properties which readily permit studies that would be difficult or impossible to interpret in other systems. Furthermore, preliminary studies indicate that the somatostatin receptor in these two cell lines are different. The following aspects of somatostatin action will be examined: 1. Mechanisms by which somatostatin regulates intracellular free Ca2+ concentrations and the importance of the induced changes in cytosolic free Ca2+ in mediating somatostatin inhibition of secretion. 2. Regulation of the binding and transduction properties of the somatostatin receptor. 3. MEchanisms by which somatostatin action is terminated. 4. Comparison of the binding properties, ligand processing capabilities and structures of somatostatin receptors in endocrine and neural target cells. A minor objective of this research plan is to examine the regulation of pituitary function by the neurotransmitter adenosine. Therefore the effects of adenosine receptor agonists and antagonists on pituitary hormone secretion will be determined in primary cultures. In addition, the intracellular mediators involved in adenosine action will be examined in the clonal pituitary cell line.