NEUROPEPTIDE AND TRANSMITTER ACTION IN SECRETORY CELLS

拟议的研究旨在了解分子事件 参与细胞功能抑制调节剂的作用， 与靶细胞受体的初始相互作用， 减少分泌的反应。 本研究的主要目的是 计划是研究神经肽生长抑素 在不同的靶细胞中发挥作用。 拟议的研究将 着重于生长抑素在两种克隆细胞系中的作用： 来源于垂体前叶的内分泌细胞系和 神经母细胞瘤衍生的细胞株。 这些细胞保留了许多 分化的功能的组织的起源，并拥有几个独特的 容易允许研究的性质， 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 不同. 将对生长抑素作用的以下方面进行研究： 1.生长抑素调节细胞内游离钙离子的机制 浓度和诱导的细胞质游离 Ca ~（2+）介导生长抑素的分泌抑制。 2.调节蛋白质的结合和转导特性 生长抑素受体 3.生长抑素作用终止的机制。 4.结合特性、配体加工能力和 内分泌和神经靶细胞中生长抑素受体的结构。 本研究计划的一个次要目标是研究 脑下垂体的功能通过神经递质腺苷。 因此 腺苷受体激动剂和拮抗剂对垂体激素的影响 将在原代培养物中测定分泌。 此外该 涉及腺苷作用的细胞内介质将在 克隆垂体细胞系。

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.