OPIOID PEPTIDE GENE EXPRESSION IN NUCLEUS CAUDALIS

尾核中阿片肽基因的表达

• 批准号: 3412805
• 负责人: Michael A. Moskowitz
• 金额: $ 17.97万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-12-01 至 1992-12-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3412805
• 关键词: afferent nerve; caudate nucleus; cell population study; dynorphins; enkephalins; gene expression; genetic regulation; in situ hybridization; inhibitor /antagonist; laboratory rat; messenger RNA; opioid receptor; oral facial pain; periaqueductal gray matter; stimulant /agonist

Nucleus caudalis neurons that express the opioid peptide neurotransmitter genes preproenkephalin and preprodynorphin are prominently implicated in the modulation of dental and other orofacial pain by primary afferent inputs, descending brainstem systems, and even by opiate drugs. However, the details of these interactions and the differential roles that peptides derived from each of these genes might play in these processes remain obscure. This proposal will utilize recently-developed in situ hybridization techniques to quantitatively assess the relative levels of expression of these two genes in nucleus caudalis neurons. It will confirm the specific patterns of alterations in the neuronal expression of each of these genes that we have found after removal or stimulation of the trigeminal nerve in preliminary studies. These results provide intriguing evidence for opposite changes in expression of preproenkephalin and preprodynorphin in specific neuronal subpopulations in response to removal of primary afferents, and of differential cellular responses to stimulation of fibers of different diameters. Influences of stimulation of the descending painsuppressing pathways originating from the periaqueductal grey will also be evaluated. Finally, the impact of the opiate agonist and antagonist drugs that have been found in our laboratories to modulate expression of these genes in striatal neurons will be assessed in neurons of the nucleus caudalis. These changes in neuronal mRNA levels could indicate altered rates of release of peptides from neurons expressing each of the genes if the rates of translation, processing, intracellular transport and degradation and the size of peptide stores were stable in these settings. This information will enhance appreciation of the complex but potentially powerful impact of these stimuli on the function of the nucleus caudalis neurons that provide a crucial first level of modulation of dental and orofacial pain.

表达阿片肽的尾侧核神经元 神经递质基因前脑啡肽原和前强啡肽原是 突出地牵涉到调整牙齿和其他 初级传入、下行脑干引起的口面部疼痛 系统，甚至通过鸦片类药物。然而，这些细节 多肽的相互作用及其不同作用 这些基因中的每一个都可能在这些过程中发挥作用，但目前还不清楚。 这项提议将利用最近发展起来的原位杂交 定量评估相对水平的技术 这两个基因在尾侧核神经元中的表达。会的 确认神经元变化的特定模式 我们在移除后发现的每一个基因的表达 或在初步研究中刺激三叉神经。 这些结果提供了耐人寻味的证据，证明了 前脑啡肽原和前强啡肽原在特异性肿瘤中的表达 原发灶摘除后神经元亚群的变化 传入和细胞对刺激的不同反应 不同直径的纤维。刺激性心理障碍的影响 下行疼痛抑制通路起源于 导水管周围的灰色也将被评估。最后，影响 已发现的阿片激动剂和拮抗剂药物 我们的实验室调节这些基因在纹状体中的表达 将对尾侧核的神经元进行评估。 这些神经细胞信使核糖核酸水平的变化可能表明心率的改变。 表达每种基因的神经元释放的多肽 如果翻译、处理、细胞内传输的速度 降解率和多肽库的大小都是稳定的 设置。这一信息将加强对 这些刺激的复杂但潜在的强大影响 尾核神经元的功能提供了至关重要的 牙齿和口腔面部疼痛的第一级调制。