Aminergic control of early devlopment

神经递质5-羟色胺（5-HT，5-羟色胺）的功能在中枢神经系统和一些其他组织中被深入研究和熟知。 5-HT及其受体在雌性生殖组织中的存在在脊椎动物中已被零星报道，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如冲浪蛤中。 在该物种中，5-HT触发成熟动物的产卵，并在加入到分离的卵母细胞中时诱导卵母细胞减数分裂成熟，从而模仿通常由精子激活的过程。 使用冲浪蛤作为模型，我们以前已经表明，他们的前期I-逮捕卵母细胞具有5-HT受体，其激活触发增加细胞内钙和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卵母细胞5-HT受体，通过研究其信号传导特性和药理学概况时，转染在哺乳动物宿主细胞（HEK-293），并确定它是否是特定的受体导致减数分裂成熟。 其他胺能受体表达的蛤卵母细胞将进行调查，包括克隆的假定章鱼胺受体，并测试其影响减数分裂成熟的能力。 我们还将验证在何种程度上观察到的cAMP上升引起的5-HT是因果关系在静止卵母细胞减数分裂的重新启动。 我们将研究特定的激活剂和抑制剂的蛋白激酶A的能力，改变减数分裂重新启动5-HT和建立可能的内部cAMP水平和MAPK信号通路之间的联系，相对于细胞内钙升高。 最后，其他生物胺，如章鱼胺和多巴胺在生殖调节的可能参与将被检查。 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。 我们的工作将铺平道路，了解潜在的作用，越来越多的名单胺能受体的未知的局部功能，但据报道，不仅在无脊椎动物，但脊椎动物物种的生殖细胞中表达，以及。

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.