REGULATION OF CGMP IN THE MANDUCA SEXTA OLFACTORY SYSTEM

描述：（改编自研究者摘要） 信使cGMP对多种功能都很重要。它是由 鸟苷酸环化酶（GC）。GC以多种形式存在， 分类为受体（膜结合）或可溶性。增加 通过GC的激活在环鸟苷酸水平上的作用被认为很重要 调节许多不同的病理生理学途径 重要性，包括偏头痛，阳痿和哮喘。cGMP也参与其中 在神经元可塑性，包括LTP和LTD，适应的水平， 嗅觉受体神经元和视觉信号转导等。这 本申请提出通过以下方法研究cGMP在神经系统中的作用： 研究环鸟苷酸调节机制的嗅觉系统的曼陀罗 sexta，一个实验上有利的模型系统，其中解剖和 电生理学研究得很好。本提案中所述的研究将 对了解cGMP在肿瘤中的作用具有重要意义。 嗅觉系统，一般的神经系统，最后是任何系统 其中cGMP在介导细胞通信和功能中起作用。 PI建议解决嗅觉中鸟苷酸环化酶的调节 通过回答以下问题，作为具体目标，了解Manduca sexta系统： (1)触角叶中的哪些神经元能够并且确实对NO作出反应？一氧化氮 (NO)是可溶性GC的有效刺激物。(2)的作用是什么 触角叶的NO/sGC系统？这一具体目标审查了 NO/sGC的药理学操作用于行为或 触角叶的电生理输出。(3)活动如何 新的GC，MsGC-1，在嗅觉系统中的调节功能， 曼陀罗花？MsGC-1是一种新型的GC，其表达模式表明 它在嗅觉中cGMP的介导中起着重要作用， 系统(4)曼杜卡的嗅觉系统中还表达了哪些GC sexta？PI有证据表明至少有四种以上的GC在嗅觉中表达， 系统PI建议克隆这些并检查它们在调解中的作用 嗅觉系统中的环鸟苷酸水平。

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.