CYCLIC GMP AND PHOTORECEPTOR FUNCTION

描述(改编自申请人的摘要)：环状GMP(CGMP)是 视觉和视网膜光感受器的主要细胞内信使。CGMP 是由一种视网膜磷酸二酯酶(PDE)调节的，而这一焦点 应用于，详细研究PDE调节的生物化学 活动。应用的具体目的是：(1)研究构象 CGMP或其抑制γ结合后杆状PDE结构的变化 亚基；(2)确定新的通路是否不同于转导 在恢复或适应过程中激活/失活调节杆状PDE； 确定杆状和锥状PDE的催化位置的决定因素 用于结合环核苷酸底物或药物抑制物 酶；以及(4)检验视杆细胞和视锥细胞的生理差异 反应性可以部分归因于激活和激活的差异 在视锥感光细胞中发现的PDE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.