PHARMACOLOGY OF AQUEOUS OUTFLOW IN THE HUMAN EYE

描述（改编自申请人摘要）： 拟议的研究是为了获得进一步的生理学知识， 人类眼睛中房水流出的药理学。《世界人权宣言》 拟议的研究是表征cAMP在介导变化中的作用， 在流出设施中，总的假设是， 一个以上的环化酶参与介导的反应， 流出系统对肾上腺素，肾上腺素， 毒蕈碱激动剂和Na/K/2Cl共转运调节剂。的 具体目标包括：（1）腺苷酸的异构体的鉴定 人流出道组织环化酶及其药理学特征 人流出组织中cAMP介导的流出;（2）药理学 毒蕈碱类药物的外流便利性增强作用的表征 其在体外直接发生在人流出组织上， 独立的睫状肌，和映射的亚型， 流出途径中的毒蕈碱受体;和（3）药理学 内皮样血管生成素亚型的表征和鉴定 Na/K/2Cl共运输系统，最近在外流中描述 组织.拟议中的研究将利用生理、生物化学、 和分子生物学方法，提供了一个更完整的 对人眼中的房水流出的调节的理解。 加强对正常外流的基本机制的了解 可能有助于了解原发性开角型青光眼的发病机制， 促进改进治疗方法的发展。

DESCRIPTION (Adapted from applicant's abstract): The overall goal of the proposed research is to gain further knowledge of the physiology and pharmacology of aqueous outflow in the human eye. A major emphasis in the proposed studies is to characterize the role of cAMP in mediating changes in outflow facility, with an overall hypothesis that there is probably more than one cyclase involved in mediating the responsiveness of the outflow system to such diverse stimuli as epinephrine, prostaglandins, muscarinic agonists and modulators of Na/K/2Cl co-transport. The specific aims include: (1) identification of isoforms of adenylate cyclase in human outflow tissue and pharmacological characterization of cAMP-mediated outflow in human outflow tissue; (2) pharmacological characterization of the outflow facility increasing-effect of muscarinics which occurs directly on human outflow tissue in vitro and is independent of the ciliary muscle, and mapping of the subtypes of muscarinic receptors in the outflow pathways; and (3) pharmacological characterization and identification of isoforms of the endothelial-like Na/K/2Cl co-transport system which has recently been described in outflow tissue. The proposed studies will make use of physiological, biochemical and molecular biological methods in providing a more complete understanding of the regulation of aqueous outflow in the human eye. Enhanced understanding of the basic mechanisms underlying normal outflow may lend insight into the pathogenesis of primary open angle glaucoma and facilitate development of improved treatments.