Aminergic control of early devlopment

早期发育的胺能控制

• 批准号: 180585-2006
• 负责人: Dubé, François
• 金额: $ 2.99万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2006
• 资助国家: 加拿大
• 起止时间: 2006-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=337077
• 关键词: Aminergic; control; early; devlopment

The functions of the neurotransmitter serotonin (5-HT, 5-hydroxytryptamine) are intensively studied and well known in the central nervous system and some other tissues.  The presence of 5-HT and its receptors in female reproductive tissues has been sporadically reported in vertebrate animals but it is in some invertebrates that precise functions of 5-HT in reproduction have been better described, in particular in molluscan species such as surf clam.  In this species, 5-HT triggers spawning in mature animals, and induces oocyte meiotic maturation when added to isolated oocytes, thus mimicking a process of activation normally set by the fertilizing sperm.  Using surf clam as a model, we have previously shown that their prophase I-arrested oocytes possess a 5-HT receptor whose activation triggers increased intracellular calcium and cAMP, and leads to full meiotic maturation.  Our specific objectives will be to further characterize a cloned putative clam oocyte 5-HT receptor by studying its signalling properties and pharmacological profile when transfected in mammalian host cells (HEK-293), and determine whether it is the specific receptor leading to meiotic maturation.   Other aminergic receptors expressed in clam oocytes will be investigated, including a cloned putative octopamine receptor, and tested for their capacity to influence meiotic maturation.  We will also verify to what extent observed cAMP rises elicited by 5-HT are causal in reinitiating meiosis in quiescent oocytes.  We will examine the capacity of specific activators and inhibitors of protein kinase A to alter meiosis reinitiation by 5-HT and establish possible links between internal cAMP levels and the MAPK signaling pathway relative to intracellular calcium rises.  Finally, the possible involvement of other biogenic amines such as octopamine and dopamine in the regulation of reproduction will be examined.  Our research program will clarify the mechanisms by which aminergic receptors are involved in reproductive and early developmental processes.  Our work will pave the way for understanding potential roles of a growing list of aminergic receptors of unknown local function but reported to be expressed in reproductive cells of not only invertebrate but vertebrate species, as well.

神经递质血清素的功能5-羟色胺（5-HT，5-hydroxytryptamine）在中枢神经系统和其他组织中被广泛研究和熟知，5-HT及其受体在脊椎动物雌性生殖组织中的存在已被零星报道，但在某些无脊椎动物中，5-HT在生殖中的精确功能已被更好地描述，特别是在软体动物物种中，如冲浪蛤。在这种物种中，5-HT触发成熟动物的产卵，当加入到分离的卵母细胞中时，诱导卵母细胞减数分裂成熟，从而模拟通常由精子激活的过程。使用冲浪蛤作为模型，我们先前已经表明它们的前期I停滞的卵母细胞具有5-HT受体，其激活触发增加的细胞内钙和cAMP，并导致完全减数分裂成熟。我们的具体目标将是进一步表征克隆的推定蛤蜊卵母细胞5-通过研究HT受体在哺乳动物宿主细胞（HEK-293）中转染时的信号传导特性和药理学特征，确定其是否是导致减数分裂成熟的特异性受体。 将研究在蛤卵母细胞中表达的其他胺能受体，包括克隆的推定章鱼胺受体，并测试它们影响减数分裂成熟的能力。我们还将验证观察到的5-HT引起的cAMP升高在多大程度上导致静止卵母细胞重新启动减数分裂。我们将检查蛋白激酶A的特异性激活剂和抑制剂改变5-HT减数分裂重新启动的能力。HT和建立内部cAMP水平和MAPK信号通路之间的可能联系，相对于细胞内钙升高。本研究将探讨其他生物胺如章鱼胺和多巴胺在生殖调控中的可能作用。我们的研究计划将阐明胺能受体参与生殖和早期发育过程的机制。我们的工作将为研究了解潜在作用的方式越来越多的名单胺受体未知的地方功能，但据报道，不仅在无脊椎动物，但脊椎动物物种的生殖细胞表达，以及。