Regulation of Vasopressin Secretion

加压素分泌的调节

• 批准号: 7883281
• 负责人: CELIA D SLADEK
• 金额: $ 37.37万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7883281
• 关键词: AMPA Receptors; Adenosine; Adrenergic Receptor; Afferent Pathways; American; Arousal; Binding; Blood Volume; Brain Stem; Cells; Chemosensitization; Complex; Coupling; Cyclic AMP-Dependent Protein Kinases; Data; Evaluation; Exposure to; Figs - dietary; Funding; Gene Expression; Genetic Transcription; Goals; Grant; Heart; Hemorrhage; Hormones; Hour; Hypothalamic structure; Imaging Techniques; Life; Lobe; MAP Kinase Gene; Mediating; Metabolism; Neurons; Neurotransmitters; Norepinephrine; Osmolalities; P2X-receptor; Pattern; Phenylephrine; Protein Kinase C; Proteins; Publications; Purinoceptor; Regulation; Role; Signal Transduction; Signaling Molecule; System; Testing; Vasopressins; Work; desensitization; pressure; prevent; receptor; receptor coupling; relating to nervous system; research study; response; rho; supraoptic nucleus; synergism

Two years of support for this project will allow us to perform the experiments proposed in Aims 3 and 4 of the original application. We have been able to complete the bulk of Aims 1 and 2 with support from the American Heart Assoc. This supported our hypothesis that simultaneous exposure of supraoptic neurons (SON) to ATP and phenylephrine induces a shift to non-desensitizing ionotropic purinergic receptor subtypes that allow ATP to sustain vasopressin (VP) release for hours. This work has been submitted for publication. The AHA grant does not provide support for Aims 3 and 4 which are crucial to understanding the mechanism by which norepinephrine can induce the shift in purinergic receptor subtype: Aim 3 is focused on identifying the 1-adrenergic receptor subtype activated by phenylephrine in SON and Aim 4 will identify the signal cascades activated by phenylephrine in SON. Identifying the 1-R signal cascade is critical to understanding why ATP activation of metabotropic purinergic receptors does not induce the same effect as phenylephrine. The ability of phenylephrine to induce sustained responses to ATP is important, because it provides a mechanism for homeostatic CNS regulatory systems to mount extended responses in order, for example, to restore blood volume following hemorrhage or for sustained arousal.

这个项目两年的支持将使我们能够执行原始申请的目标3和目标4中提出的实验。在美国心脏协会的支持下，我们已经完成了目标1和目标2的大部分。这支持了我们的假设，即视上神经元（SON）同时暴露于ATP和苯肾上腺素诱导向非脱敏的嗜离子嘌呤能受体亚型转变，使ATP维持抗利尿激素（VP）释放数小时。这项工作已提交出版。美国心脏协会的资助不支持Aims 3和4，这对理解去甲肾上腺素诱导嘌呤能受体亚型转变的机制至关重要：Aims 3的重点是鉴定SON中由苯肾上腺素激活的1-肾上腺素能受体亚型，Aim 4将鉴定SON中由苯肾上腺素激活的信号级联。确定1-R信号级联对于理解为什么ATP激活代谢嘌呤能受体不会诱导与苯肾上腺素相同的效果至关重要。苯肾上腺素诱导对ATP的持续反应的能力很重要，因为它提供了一种机制，使体内平衡的中枢神经系统调节系统能够产生延长的反应，例如，在出血后恢复血容量或持续唤醒。

项目成果

Estrogen receptor-alpha expression in osmosensitive elements of the lamina terminalis: regulation by hypertonicity.

终板渗透敏感元件中雌激素受体α的表达：高渗调节。

• DOI: 10.1152/ajpregu.00136.2004
• 发表时间: 2004
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Somponpun,SuwitJ;Johnson,AlanKim;Beltz,Terry;Sladek,CeliaD
• 通讯作者: Sladek,CeliaD

Dehydration induces Fos, but not increased vasopressin mRNA in the supraoptic nucleus of aged rats.

脱水会诱导老年大鼠视上核中的 Fos，但不会增加加压素 mRNA。

• DOI: 10.1016/0006-8993(94)90229-1
• 发表时间: 1994
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Sladek,CD;Olschowka,JA
• 通讯作者: Olschowka,JA

ATP increases intracellular calcium in supraoptic neurons by activation of both P2X and P2Y purinergic receptors.

ATP 通过激活 P2X 和 P2Y 嘌呤受体来增加视上神经元的细胞内钙。

• DOI: 10.1152/ajpregu.00495.2006
• 发表时间: 2007
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Song,Zhilin;Vijayaraghavan,Sukumar;Sladek,CeliaD
• 通讯作者: Sladek,CeliaD

Osmotic regulation of estrogen receptor-beta expression in magnocellular vasopressin neurons requires lamina terminalis.

大细胞加压素神经元中雌激素受体β表达的渗透调节需要终板。

• DOI: 10.1152/ajpregu.00478.2003
• 发表时间: 2004
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Somponpun,SuwitJ;Johnson,AlanKim;Beltz,Terry;Sladek,CeliaD
• 通讯作者: Sladek,CeliaD

Integration of thermal and osmotic regulation of water homeostasis: the role of TRPV channels.

• DOI: 10.1152/ajpregu.00270.2013
• 发表时间: 2013-10
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: C. Sladek;A. Johnson