REGULATION OF CGMP IN THE MANDUCA SEXTA OLFACTORY SYSTEM

MANDUCA Sexta 嗅觉系统中 CGMP 的调节

• 批准号: 6516234
• 负责人: ALAN J NIGHORN
• 金额: $ 23.58万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6516234
• 关键词: Manduca; age difference; circadian rhythms; complementary DNA; conditioning; cyclic GMP; enzyme activity; enzyme induction /repression; ethology; guanylate cyclase; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; isozymes; molecular cloning; nitric oxide; northern blottings; odors; olfactions; pheromone; polymerase chain reaction; tissue /cell culture

DESCRIPTION: (Adapted from the Investigator's Abstract) The intracellular messenger cGMP is important for a wide variety of functions. It is generated by the enzyme guanylyl cyclase (GC). GCs exist in multiple forms and are classified as being either receptor (membrane associated) or soluble. Increases in the level of cGMP through the activation of GCs is thought to be important for the regulation of many different pathways with pathophysiological significance, including migraine, impotence, and asthma. cGMP is also involved in neuronal plasticity including LTP and LTD, adaptation at the level of the olfactory receptor neurons, and visual signal transduction among others. This application proposes to investigate the role of cGMP in the nervous system by examining the mechanisms of cGMP regulation in the olfactory system of Manduca sexta, an experimentally favorable model system in which the anatomy and electrophysiology are well studied. The studies described in this proposal will have significance for the understanding of the function of cGMP in the olfactory system, in the nervous system in general, and finally in any system in which cGMP plays a role in mediating cellular communication and function. The PI proposes to address the regulation of guanylyl cyclases in the olfactory system of Manduca sexta by answering the following questions as specific aims: (1) Which neurons in the antennal lobe can and do respond to NO? Nitric oxide (NO) is a potent stimulator of soluble GCs. (2) What is the function of the NO/sGC system in the antennal lobe? This specific aim examines the effects of pharmacological manipulation of the NO/sGC for either behavioral or electrophysiological outputs of the antennal lobe. (3) How is the activity of the function of the novel GC, MsGC-1, regulated in the olfactory system of Manduca sexta? MsGC-1 is a new type of GC whose expression pattern suggests that it plays an important role in the mediation of cGMP in the olfactory system. (4) What other GCs are expressed in the olfactory system of Manduca sexta? The PI has evidence of at least four more GCs expressed in the olfactory system. The PI proposes to clone these and examine their roles in mediating cGMP levels in the olfactory system.

描述：（改编自研究者摘要）细胞内 信使 cGMP 对于多种功能都很重要。它是由 鸟苷酸环化酶（GC）。 GC 有多种形式存在， 分为受体（膜相关）或可溶性。增加 通过 GC 的激活来提高 cGMP 水平被认为是重要的 用于调节许多不同的病理生理途径 重要性，包括偏头痛、阳痿和哮喘。 cGMP也参与其中 神经元可塑性，包括 LTP 和 LTD，适应水平 嗅觉受体神经元和视觉信号转导等。这 申请提出通过以下方式研究 cGMP 在神经系统中的作用 检查 Manduca 嗅觉系统中 cGMP 调节机制 sexta，一个实验上有利的模型系统，其中的解剖学和 电生理学得到了很好的研究。本提案中描述的研究将 对于了解 cGMP 的功能具有重要意义 嗅觉系统，一般神经系统，最后是任何系统 其中 cGMP 在介导细胞通讯和功能中发挥作用。 PI 建议解决嗅觉中鸟苷酸环化酶的调节问题 Manduca sexta 系统通过回答以下问题作为具体目标： (1) 触角叶中的哪些神经元可以并且确实对 NO 做出反应？一氧化氮 (NO) 是可溶性 GC 的有效刺激剂。 (2) 其作用是什么 NO/sGC 系统位于触角叶吗？这一具体目标考察了以下因素的影响： NO/sGC 的药理学操作可用于行为或 触角叶的电生理输出。 （三）活动情况如何 新型 GC MsGC-1 的功能在嗅觉系统中受调节 烟草天蛾？ MsGC-1是一种新型GC，其表达模式表明 它在嗅觉中 cGMP 的介导中起重要作用 系统。 (4) 烟草天蛾的嗅觉系统中还表达了哪些其他GC 六号？ PI 有证据表明嗅觉中至少还有 4 个 GC 表达 系统。 PI 建议克隆这些并检查它们在调解中的作用 嗅觉系统中的 cGMP 水平。