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Integrating Osmosensitivity and Autocrine Signaling in a Model for Osmoregulation.

将渗透敏感性和自分泌信号整合到渗透调节模型中。

基本信息

批准号：
9225054
负责人：
Andre P. Seale
金额：
$ 15.07万
依托单位：
UNIVERSITY OF HAWAII AT MANOA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-16 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9225054
关键词：
Accounting Address Autocrine Communication Binding Biological Models Businesses Cell Line Cell Volumes Cell model Cell physiology Cells Clinical Medicine Coma Congestive Heart Failure Convulsions Development Direct Costs Electrolyte Disorder Endocrine Endocrine system Equilibrium Failure Feedback Fishes Functional disorder Future Gene Activation Genes Goals Homeostasis Hormonal Hormones Human Hypernatremia Hyponatremia Incubated Intervention Investigation Ion Transport Ions Knowledge Lead Life Ligands Maintenance Measures Mediating Mediation Medical Modality Modeling Nature Neurosecretory Systems Oreochromis mossambicus Osmolalities Osmoregulation Output Pathology Pathway interactions Patients Physiological Pituitary Gland Pituitary Hormones Plasma Prolactin Prolactin Receptor Protein Isoforms Radioimmunoassay Regulation Research Sensory Signal Transduction Signal Transduction Pathway Sodium Chloride Stimulus Stretching Structure Therapeutic Intervention Tilapia Tissues Vertebrates Water autocrine body system channel blockers clinical practice experience extracellular falls inhibitor/antagonist insight macromolecule novel osmoreceptor paracrine peptide hormone receptor binding response steroid hormone teleost tool water channel

项目摘要

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.

项目摘要-摘要