Characterization and function of a novel receptor in smooth muscle cells

被称为受体的蛋白质存在于细胞表面。化合物与受体结合，引起细胞反应，调节组织和器官的正常功能。受体是多样的，它们的重要性因细胞类型而异。例如，在血管中，平滑肌细胞调节血液流动，在向器官输送氧气和营养方面发挥重要作用。在血管中，平滑肌上的受体会导致血管缩短或收缩，从而增加对血流的阻力。超过80%的药物针对的受体类似于存在于平滑肌细胞表面的受体。对于许多受体来说，激活受体的化学物质(配体)的身份是未知的。我们称之为后一种类型的孤儿受体。确定孤儿受体的配体是制药业用来开发新药物实体的一种策略。因此，识别孤儿受体的配体可能是一项重大的科学发现，可能会对研究界和社会产生长期影响。 我们NSERC研究的目标是研究一种新的受体，通过观察它如何导致血管收缩，从而改变整个生物体的血液流动。我们还将使用这些信息来查看是否在其他地方发现了该受体，并确定其在其他组织和系统中的功能。 在之前发表的工作中，我们发现了一种新的受体，它在血管平滑肌细胞功能中发挥作用。这种受体引起血管收缩，预计会增加血压，减少流向器官的血流量。这个程序特别新颖的是，受体的身份和与配体(测试化合物)相关的生物活性范围尚未确定。 我们将进行实验室实验，利用从小鼠血管中分离的细胞来鉴定受体，并描述导致平滑肌收缩的生化机制。为了证明我们的结果对整个有机体(生理重要性)具有意义，我们将在活体动物中进行测试，以研究一种激活收缩机制的化合物。更多的实验将被用来进一步表征该受体在血管组织中的活性和功能；随后将在其他组织中进行。 该计划将支持培训高素质的博士科学家，这些科学家将极有可能做出具有广泛科学影响的原创性发现。这些人将拥有技能，使他们高度适应未来不同的研究环境，无论是在学术界还是在行业研究中，并将在领先的研究团队中拥有经验。 该计划将建立关于细胞受体的实验室基础科学证据，这可能导致为未来的技术转移和商业化创造新材料。

Proteins called receptors are on the surfaces of cells. Chemical compounds bind to receptors and cause cell responses that regulate the normal function of tissues and organs. Receptors are diverse and their importance varies according to the type of cell. For example, in blood vessels the smooth muscle cells regulated blood flow, an important role in oxygen and nutrient delivery to organs. In blood vessel the receptors on smooth muscle can cause them to shorten or contract, which increases the resistance to blood flow. More than 80% of pharmaceutical drugs target receptors like those present on the surface of smooth muscle cells. For many receptors, the identity of the chemicals (ligands) that activate the receptor are unknown. We call these latter type orphan receptors. Identifying the ligands for orphan receptors is one strategy being used by the pharmaceutical industry to develop new drug entities. Therefore, identifying the ligands for an orphan receptor can be a significant scientific discovery that can have long-term impact on the research community and society. The goal of our NSERC research is to study a novel receptor by looking at how it causes blood vessel contraction and thereby changes blood flow in whole organisms. We will also use this information to see whether the receptor is found elsewhere and to determine its function in those other tissues and systems. In previously published work, we identified a novel receptor that has a role in vascular smooth muscle cell function. This receptor causes blood vessel constriction, which would be anticipated to increase blood pressure and decrease blood flow to organs. What is particularly novel about this program is that the identity of the receptor and the scope of biological activities associated with the ligand (test-compound) have not been determined. We will conduct lab experiments to identify the receptor and describe the biochemical mechanisms that cause smooth muscles to contract by using cells isolated from blood vessels of mice. To show that our results have meaning for the whole organism (the physiological importance), we will conduct testing in live animals to study a compound that activates the contraction mechanism. Additional experiments will be used to further characterize the activity and function of this receptor in vascular tissues first; later in other tissues. This program will support the training of highly-qualified PhD scientists that will be highly likely to make original discoveries with broad scientific impact. These people will have skills to make them highly adaptable to different future research environments either in academia or industry research and will have experience with leading research teams. This program will establish laboratory basic science evidence about a cell receptor that may lead to creation of new materials for future technology transfer and commercialization.