CYCLIC GMP AND PHOTORECEPTOR FUNCTION

描述（改编自申请人摘要）：cGMP是 视觉和视网膜光感受器的主要细胞内信使。的cGMP 是由视网膜磷酸二酯酶（PDE）调节的，这一点的重点是 应用是详细研究PDE调节的生物化学 活动具体目的是：（1）研究构象 cGMP或其抑制性γ结合后杆PDE结构的变化 亚基;（2）确定是否有不同于转导的新途径 激活/失活调节恢复或适应过程中的杆PDE;（3） 确定决定因素在催化网站的杆和锥PDE负责 用于结合环核苷酸底物或药物抑制剂， 酶;（4）测试杆和锥中的生理差异 反应性可以部分归因于激活和 在视锥细胞感光器中发现的PDE的不同亚型的调节。

Description (Adapted from the applicant's abstract): Cyclic GMP (cGMP) is the primary intracellular messenger for vision and retinal photoreceptors. The cGMP is regulated by a retinal phosphodiesterase (PDE), and the focus of this application is to study, in detail, the biochemistry of the regulation of PDE activity. The specific aims of the application are: (1) to study conformational changes of rod PDE structure upon binding of cGMP or its inhibitory gamma subunit; (2) to determine whether novel pathways distinct from transducin activation/inactivation regulate rod PDE during recovery or adaptation; (3) to identify the determinants at the catalytic site of rod and cone PDE responsible for binding cyclic nucleotide substrates or pharmacological inhibitors of the enzyme; and (4) to test the idea that physiological differences in rod and cone responsiveness can be ascribed in part to differences in the activation and regulation of the distinct isoform of PDE found in cone photoreceptors.