PREJUNCTIONAL RECEPTORS IN THE ANTERIOR UVEA

前 UVEA 中的交界前受体

• 批准号: 2159368
• 负责人: James Jumblatt
• 金额: $ 18.51万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2159368
• 关键词: G protein; adenylate cyclase; alpha adrenergic receptor; binding proteins; biomarker; calcium channel blockers; chromatography; cyclic AMP; dopamine receptor; eye agent; eye pharmacology; guanosine triphosphate; human tissue; immunologic assay /test; iris; laboratory rabbit; muscarinic receptor; nerve endings; neural information processing; neural transmission; neurotransmitter transport; neurotransmitters; norepinephrine; ocular hypotensive; prostaglandin E; prostaglandin receptor; radioassay; second messengers; secretion; sympathetic nervous system; uvea ciliary body

The overall objective of this project continues to be an understanding of the prejunctional mechanisms that control sympathetic neurotransmission in the anterior segment of the eye. Agents that modify sympathetic neurotransmitter release have potential usefulness in glaucoma therapy. In rabbit studies, we have identified a variety of prejunctional inhibitory and facilitatory receptors that modulate norepinephrine secretion in the isolated, superfused iris-ciliary body and excised ciliary processes. We will determine, in each case, whether a pharmacological basis exists for selective manipulation of prejunctional or postjunctional uveal receptors of the same type. We will evaluate the hypothesis that prejunctional inhibitory receptors of different types share a common mechanism - decreased cAMP formation - for inhibition of norepinephrine release. The role of GTP-binding (G) proteins in receptor-mediated regulation of neurosecretion and/or adenylate cyclase will be evaluated and correlated. Using newly developed in vitro techniques, we will identify and characterize prejunctional receptors that modulate sympathetic neurosecretion in the human iris and ciliary body. The results of these studies will improve our knowledge of the pharmacologically accessible targets for regulation of sympathetic neurotransmission in the eye, and will establish their potential relevance to human ocular pharmacology, particularly with regard to glaucoma therapy.

该项目的总体目标仍然是了解 控制交感神经传递的预连接机制 眼睛的前段。 修改交感神经的药物 神经递质释放在青光眼治疗中具有潜在用途。 在 兔子研究中，我们发现了多种结前抑制 以及调节去甲肾上腺素分泌的促进受体 分离的、灌注的虹膜睫状体和切除的睫状体。 我们 将在每种情况下确定是否存在药理学基础 选择性操纵结前或结后葡萄膜受体 属于同一类型。 我们将评估假设 不同类型的抑制性受体具有共同的机制 - 减少 cAMP 形成 - 抑制去甲肾上腺素释放。 这 GTP 结合 (G) 蛋白在受体介导的调节中的作用 将评估和关联神经分泌和/或腺苷酸环化酶。 使用新开发的体外技术，我们将识别和 表征调节交感神经的连接前受体 人类虹膜和睫状体的神经分泌。 这些结果 研究将提高我们对药理学可及性的了解 调节眼睛交感神经传递的目标，以及 将确定它们与人眼药理学的潜在相关性， 特别是在青光眼治疗方面。

项目成果

Cholinergic inhibition of adrenergic neurosecretion in the rabbit iris-ciliary body.

兔虹膜睫状体中肾上腺素能神经分泌的胆碱能抑制。

• 发表时间: 1988
• 期刊: Investigative ophthalmology & visual science
• 影响因子: 4.4
• 作者: Jumblatt,JE;North,GT
• 通讯作者: North,GT

Prejunctional receptors and second messengers for angiotensin II in the rabbit iris-ciliary body.

兔虹膜睫状体内血管紧张素 II 的连接前受体和第二信使。

• DOI: 10.1006/exer.1993.1143
• 发表时间: 1993
• 期刊: Experimental eye research
• 影响因子: 3.4
• 作者: Ohia,SE;Jumblatt,JE
• 通讯作者: Jumblatt,JE

Prejunctional inhibitory effects of prostanoids on sympathetic neurotransmission in the rabbit iris-ciliary body.

前列腺素类药物对兔虹膜睫状体交感神经传递的预抑制作用。

• 发表时间: 1990
• 期刊: The Journal of pharmacology and experimental therapeutics
• 作者: Ohia,SE;Jumblatt,JE
• 通讯作者: Jumblatt,JE

Neuropeptide Y modulates adenylate cyclase in the rabbit iris ciliary body and ciliary epithelium.

神经肽 Y 调节兔虹膜睫状体和睫状上皮中的腺苷酸环化酶。

• DOI: 10.1016/0014-4835(90)90077-8
• 发表时间: 1990
• 期刊: Experimental eye research
• 影响因子: 3.4
• 作者: Jumblatt,JE;Gooch,JM
• 通讯作者: Gooch,JM

Potentiation of sympathetic neurosecretion by forskolin and cyclic AMP in the rabbit iris-ciliary body.

毛喉素和环 AMP 在兔虹膜睫状体中增强交感神经分泌。

• DOI: 10.3109/02713688608996371
• 发表时间: 1986
• 期刊: Current eye research
• 影响因子: 2
• 作者: Jumblatt,JE;North,GT
• 通讯作者: North,GT