Integrating Osmosensitivity and Autocrine Signaling in a Model for Osmoregulation.

项目摘要-摘要 盐和水平衡的维持对于植物的功能稳定性至关重要。 进行生命活动的大分子。未能适当维持渗透压 平衡是几乎每个器官系统的病理的促成因素。变化 细胞外渗透压摩尔浓度由β受体检测，β受体是对β受体敏感的细胞， 能够产生一种效应物，通常是一种激素， 均衡由于对β受体的调节知之甚少， 对免疫调节效应物的免疫和免疫诱导的调节， 有前途的工具，以提高我们的基本知识，如何抵制不良监管 不平衡这种方法在以下情况下特别有价值： 这样的调节机制自然地和强烈地响应于微妙的、生理上的 适当的渗透压刺激通过采用一种可访问的鱼细胞模型， 对细胞外渗透压摩尔浓度的生理变化敏感和响应，我们试图识别 新的机制，调节神经元的接收和自分泌调节。拟议 研究包括两个主要的重叠目标：1）表征自分泌的影响， 调节一种有效的哺乳动物调节激素，罗非鱼催乳素（Prl），对Prl细胞。非鲫 细胞是一种已建立的脊椎动物内分泌模型。细胞外的下降 渗透压刺激其主要分泌产物Prl，其对靶点施加离子保持活性 调节组织。初步证据表明，两个自分泌调节 Prl的同种型受细胞外渗透压的差异调节;和2）鉴定 免疫调节自分泌调节的潜在变化机制。两个Prl 已经鉴定了受体，并显示其具有差异性的光敏性。他们的参与 在介导PRLS的自分泌调节中的作用将被重新评估。结果 从拟议的研究应提供有关监管的基本知识 受体和内分泌细胞，这可能最终导致的发展， 神经调节功能障碍的治疗干预策略。

PROJECT SUMMARY - ABSTRACT The maintenance of salt and water balance is essential to the functional stability of the macromolecules that carry on the business of life. Failure to properly maintain osmotic equilibrium is a contributing factor to the pathologies of nearly every organ system. Changes in extracellular osmolality are detected by osmoreceptors, cells that are osmosensitive and capable of producing an effector, typically a hormone, that is capable of restoring osmotic equilibrium. Because little is known about the modulation of osmoreceptors, the characterization of osmotically and hormonally induced regulation of osmoregulatory effectors represents a promising tool to advance our fundamental knowledge on how to counteract osmoregulatory disequilibrium. This approach can be especially valuable if the model for characterization of such regulatory mechanisms is naturally and strongly responsive to subtle, physiologically appropriate, osmotic stimuli. By employing an accessible fish cell model that is remarkably sensitive and responsive to physiological changes in extracellular osmolality, we seek to identify novel mechanisms that regulate osmoreception and autocrine regulation. The proposed research comprises two main overlapping goals: 1) Characterize the effects of autocrine regulation of a potent osmoregulatory hormone, the tilapia prolactin (Prl), on Prl cells. Tilapia Prl cells are an established vertebrate endocrine model for osmoreception. A fall in extracellular osmolality stimulates its main secretory product, Prl, which exerts ion-retaining activity on target osmoregulatory tissues. Preliminary evidence indicates that the autocrine regulation of two isoforms of Prl are differentially modulated by extracellular osmolality; and 2) identify the mechanism(s) underlying changes in osmotically-modulated autocrine regulation. Two Prl receptors have been identified and shown to be differentially osmosensitive. Their involvement in the mediation of autocrine regulation by Prls will be assessed pharmacologically. Findings from the proposed studies shall provide fundamental knowledge on the regulation of osmoreceptors and endocrine cells, which may ultimately lead to the development of therapeutic intervention strategies for osmoregulatory dysfunction.