ALPHA 2 AND PROSTAGLANDIN RECEPTORS IN EYE

眼睛中的 ALPHA 2 和前列腺素受体

• 批准号: 2020023
• 负责人: JOHN W. REGAN
• 金额: $ 21.04万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2020023
• 关键词: alpha adrenergic receptor; animal tissue; confocal scanning microscopy; cyclic AMP; epithelium; fluorescence microscopy; immunocytochemistry; intraocular pressure; laboratory rabbit; mitogen activated protein kinase; polymerase chain reaction; prostaglandin receptor; receptor expression; uvea ciliary body; water channel; western blottings

DESCRIPTION: The goal of this project is to understand the roles of the a2-adrenergic and prostaglandin EP receptor subtypes in the pharmacology and physiology of aqueous secretion by the mammalian ocular ciliary epithelium. Towards this end the PI will continue the work that he has started to identify the cellular and subcellular localization of the a2-adrenergic receptor subtypes in the ciliary epithelium using immunofluorescence microscopy. He will also develop antibodies to the prostaglandin EP receptor subtypes and use these in conjunction with the polymerase chain reaction for the localization of prostaglandin receptors in the ciliary epithelium. Of particular interest is the possible interaction of the a2-adrenergic and prostaglandin receptors with the functional activity of proteins that are involved with secretion, such as the Na+/K+/2C1- co-transporter and the aquaporins or water channels. In this regard, the PI has very exciting preliminary data which shows that forskolin, a modulator of intracellular cAMP, can stimulate the water permeability of aquaporin-1 and can activate a novel cationic conductance by the water channel. This suggests that receptors which can modulate intracellular cAMP formation, such as the a2-adrenergic and prostaglandin EP, can potentially regulate the activity of aquaporin-1. In fact, following heterologous expression of aquaporin-1 and prostaglandin EP2 receptors in Xenopus oocytes we can show PGE2-activation of a cationic conductance by aquaporin-1. These studies will contribute to our understanding of the regulation of aqueous secretion in the ciliary epithelium and could be potentially very important towards our understanding of the pathophysiology and treatment of glaucoma.

描述：该项目的目的是了解 药理学中的A2-肾上腺素能和前列腺素EP受体亚型 哺乳动物眼胶状上皮的水性分泌的生理学。 为此，PI将继续他开始的工作 确定A2-肾上腺素能的细胞和亚细胞定位 使用免疫荧光的睫状上皮中的受体亚型 显微镜。 他还将开发前列腺素EP的抗体 受体亚型，并将它们与聚合酶链结合使用 前列腺素受体在纤毛中定位的反应 上皮。 特别感兴趣的是A2-肾上腺素能和 具有蛋白质功能活性的前列腺素受体 与分泌物相关，例如Na+/K+/2c1-共转运蛋白和 水通道或水道。 在这方面，PI非常令人兴奋 初步数据表明，福斯科林是细胞内的调节剂 营地可以刺激水通道蛋白-1的水渗透性，并可以激活 水通道的新型阳离子电导。 这表明这一点 可以调节细胞内营地形成的受体，例如 A2-肾上腺素和前列腺素EP可以可能调节 Aquaporin-1。 实际上，aquaporin-1和 异爪蟾卵母细胞中的前列腺素EP2受体我们可以显示PGE2激活 Aquaporin-1的阳离子电导。 这些研究将有助于我们理解 睫状上皮中的水性分泌，可能非常可能 我们对理解病理生理学和治疗的重要 青光眼。