Perireceptor Contributions to Chemical Communication

周围感受器对化学通讯的贡献

• 批准号: 7275917
• 负责人: RANDALL R REED
• 金额: $ 23.89万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7275917
• 关键词: Acceleration; Address; Afferent Neurons; Aggressive behavior; Back; Behavior; Behavioral; Binding; Biological; Brain; Buffers; Chemicals; Class; Communication; Complex; Detection; Estrus Synchronization; Event; Exhibits; Genes; Genetic; Goals; Human; In Vitro; Individual; Individuality; Ligands; Liquid substance; Localized; Mammals; Mass Chromatography; Methods; Molecular Genetics; Mouse Strains; Mucous body substance; Mus; Nature; Neurons; Nose; Numbers; Odorant Receptors; Pathway interactions; Perception; Phase; Pheromone; Physiological; Play; Population; Preparation; Process; Proteins; Puberty; Research; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Role; Sensory; Sex Behavior; Sexual Arousal; Signal Transduction; Site; Social Behavior; Solid; Spectrometry; Stimulus; Structure of mucous membrane of nose; Testing; Transducers; Urine; in vivo; major urinary proteins; mutant; neuroepithelium; olfactory stimulus; prevent; programs; protein function; receptor; response; social; tool; urinary; vapor

DESCRIPTION (provided by applicant): The perception of sensory information plays a critical role in social and sexual behavior. Olfactory stimuli have been shown to elicit important responses such as intermale aggression, sexual arousal, puberty acceleration, and estrus synchronization. In many mammals, including humans, these communication stimuli have been identified as small hydrophobic, volatile molecules. These communication chemicals are present at high concentrations in biological fluids and activate specific sensory neurons by binding to specialized receptors of nasal neuroepithelia. Although there have been considerable advances in elucidating the nature of these receptors and the transduction pathway that leads to the propagation to the brain, we know very little about the critical process for managing these hydrophobic molecules in the hydrophilic nasal mucus. A specific class of lipocalins, Major Urinary Proteins (MUPs) 4 and 5 (nasal MUPs), are present in the mucus and have been shown to selectively bind a number of small hydrophobic odorants and pheromones in vitro. However, the in vivo function of the nasal MUPs as well as the other nasal lipocalins, remains unresolved largely due to the absence of molecular genetic tools. Several hypotheses have been postulated regarding their potential function including: 1. MUPs function as ligand-specific transporters delivering odorant and/or pheromones to receptor sites, 2. MUPs function as scavengers removing odorants from the receptor after transduction, 3. MUPs act as buffers preventing saturation of the receptors, and 4. MUPs act as transducers that activate the receptor. The overall hypothesis of this proposal is that nasal MUPs serve to selectively bind biologically meaningful hydrophobic molecules and are critical for odorant detection and subsequent behavior. The primary goal of this proposal is to apply integrated genetic, physiological and behavioral methods to elucidate the physiological role for nasal MUPs in mammalian chemical communication and the mechanisms whereby these compounds influence biologically relevant social behaviors. This approach to studying perireceptor events may open new avenues of research in the chemical senses and expand our understanding of normal and abnormal sensory function beyond the olfactory neuron.

描述（由申请人提供）：感官信息的感知在社会和性行为中起着至关重要的作用。嗅觉刺激已被证明可以引起重要的反应，例如男性间的攻击性、性唤起、青春期加速和发情同步。在包括人类在内的许多哺乳动物中，这些交流刺激已被确定为小的疏水性挥发性分子。这些通讯化学物质以高浓度存在于生物体液中，并通过与鼻神经上皮的特殊受体结合来激活特定的感觉神经元。尽管在阐明这些受体的性质以及导致传播到大脑的转导途径方面已经取得了相当大的进展，但我们对管理亲水性鼻粘液中这些疏水性分子的关键过程知之甚少。一类特定的脂质运载蛋白，即主要尿蛋白 (MUP) 4 和 5（鼻 MUP），存在于粘液中，并已被证明可以在体外选择性地结合许多小的疏水性气味剂和信息素。然而，鼻 MUP 以及其他鼻脂质运载蛋白的体内功能在很大程度上由于缺乏分子遗传学工具而仍未得到解决。关于其潜在功能，人们提出了几种假设，包括：1. MUP 作为配体特异性转运蛋白，将气味和/或信息素传递到受体位点，2. MUP 作为清除剂，在转导后从受体上去除气味，3. MUP 作为缓冲剂防止受体饱和，以及 4. MUP 充当激活受体的传感器。该提案的总体假设是鼻腔 MUP 可以选择性地结合具有生物学意义的疏水分子，并且对于气味检测和后续行为至关重要。该提案的主要目标是应用综合遗传、生理和行为方法来阐明鼻 MUP 在哺乳动物化学通讯中的生理作用以及这些化合物影响生物学相关社会行为的机制。这种研究感受器周围事件的方法可能会开辟化学感官研究的新途径，并扩大我们对嗅觉神经元之外的正常和异常感觉功能的理解。

项目成果

Variable selection using iterative reformulation of training set models for discrimination of samples: application to gas chromatography/mass spectrometry of mouse urinary metabolites.

• DOI: 10.1021/ac900251c
• 发表时间: 2009-07-01
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Wongravee, Kanet;Heinrich, Nina;Holmboe, Maria;Schaefer, Michele L.;Reed, Randall R.;Trevejo, Jose;Brereton, Richard G.
• 通讯作者: Brereton, Richard G.