RECEPTOR INTERACTIONS IN CILIARY PROCESSES

睫状突中受体的相互作用

• 批准号: 2161338
• 负责人: LARRY P BAUSHER
• 金额: $ 20.11万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1995-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2161338
• 关键词: adenylate cyclase; alpha adrenergic receptor; atrial natriuretic peptide; beta adrenergic receptor; binding proteins; cyclic AMP; cyclic GMP; disease /disorder model; drug interactions; drug metabolism; drug receptors; eye pharmacology; glaucoma; guanine nucleotides; hormone receptor; hormone regulation /control mechanism; human tissue; intraocular aqueous flow; intraocular fluid; intraocular pressure; laboratory rabbit; ocular hypotensive; somatostatin; uvea ciliary body; vasoactive intestinal peptide

The long term goals of the work proposed in this application are to understand receptor mediated events in the ciliary processes which may be responsible for regulation of the rate of formation of aqueous humor. Toward this end we propose to study interactions among beta2-, alpha2-, VIP, ANF, and somatostatin receptors in regulating cyclic nucleotide production by ciliary processes and examine the roles of VIP, ANF, and somatostatin in regulating aqueous flow and IOP. Most of the in vitro experiments proposed will explore cyclic AMP and cyclic GMP production by intact, excised rabbit ciliary processes; however, where significant results are obtained in this model system we will explore the possibility that similar mechanisms occur in human ciliary processes. The premise of our long term goals is that it is only by a thorough understanding of the mechanisms underlying normal regulation of aqueous flow that we will understand how some drugs currently used or proposed for use in glaucoma therapy reduce IOP and will build a logical framework within which to search for new therapeutic drugs for treatment of glaucoma. The specific aims of this proposal are to determine 1. Whether alpha2-adrenergic receptors inhibit beta2-adrenergic receptor mediated cyclic AMP production in human ciliary processes; 2. What is the nature of alpha2-adrenergic receptor-mediated inhibition of VIP-stimulated cyclic AMP production in rabbit ciliary processes; 3. What is the nature of somatostatin receptor-mediated inhibition of beta2-adrenergic and VIP receptor-mediated stimulation of cyclic AMP production in rabbit ciliary processes; 4. Whether cyclic GMP is the intracellular mediator of the ANF receptor in ciliary processes and whether ANF inhibits beta2- adrenergic and VIP receptor mediated cyclic AMP production; 5. Whether the inhibitory effects of alpha2-adrenergic and somatostatin receptors on cyclic AMP production are mediated by the guanine nucleotide binding protein Ni; 6. ANF, VIP, or somatostatin regulate aqueous flow and IOP in rabbits; 7. Whether similar mechanisms identified in rabbit ciliary processes (#2-4) occur in human ciliary processes.

本申请中提出的工作的长期目标是 了解睫状过程中的受体介导的事件 这可能是负责形成率的调节 水性幽默。 为此，我们建议学习 beta2-，alpha2-，VIP，ANF和生长抑素之间的相互作用 纤毛调节环核苷酸的受体 处理并检查VIP，ANF和生长抑素在 调节水流和IOP。 大多数体外 提出的实验将探索环状AMP和环状GMP 通过完整，切除的兔睫状工艺生产；然而， 在此模型系统中获得重大结果的地方，我们 将探讨类似机制发生的可能性 人类睫状过程。 我们长期目标的前提是 仅通过对机制的彻底理解 潜在的水流正常调节我们将 了解一些目前使用或建议用于使用的药物 青光眼疗法减少IOP，并将建立一个逻辑框架 在其中寻找新的治疗药物以治疗 青光眼。 该提案的具体目的是确定 1。α2-肾上腺素能受体是否抑制β2-肾上腺素能 受体介导的循环AMP产生人类睫状 过程； 2。α2-肾上腺素受体介导的性质是什么 抑制兔子中VIP刺激的环状AMP产生 睫状过程； 3。生长抑素受体介导的性质是什么 抑制β2-肾上腺素能和VIP受体介导的 在兔睫状过程中刺激环状AMP的产生； 4。环状GMP是否是ANF的细胞内介体 睫状过程中的受体以及ANF是否抑制beta2- 肾上腺素和VIP受体介导的环状AMP产生； 5。是否抑制α2-肾上腺素和 循环AMP产生的生长抑素受体由 鸟嘌呤核苷酸结合蛋白Ni； 6。ANF，VIP或生长抑素调节水流，并在 兔子； 7。是否在兔睫状体中鉴定出类似的机制 过程（＃2-4）发生在人类睫状过程中。