6.7.第2信使的信号通路.ppt

NO-cGMP-PKG 通路 开放钾离子通道 关闭钙离子通道 抑制内质网释放钙 PKG使MLC去磷酸化 血管平滑肌细胞舒张的典型过程 University of California-Los Angeles State University of New York in Brooklyn University of Texas Medical School in Houston. 1998 Nobel Prize Winners in Physiology or Medicine : Nobel prize committee say Yes to NO! cGMP及其激酶在心肌肥大中的作用 Nature Reviews Drug Discovery 6, 617-635 (2007) ;关注某个疾病发生发展时信号转导的变化。 cAMP和cGMP通路的关系 二者在生理效应上有一定的拮抗关系 ＋ PDE-3 AMP PDE有多种型号，分别对cAMP和cGMP特异。 Diagram illustrating possible interactions between angiotensin II- and guanylyl cyclase-dependent systems in the rat podocytes. NPR-A - guanylyl cyclase-linked receptor for ANP, sGC - soluble guanylyl cyclase, pGC - particulate guanylyl cyclase, PDE - phosphodiesterase(s) 第七章 IP3和DAG 与信号转导双信使途径 一、IP3和DAG 双信使途径 Signaling agonist 学习专业词汇！ IP3：肌醇三磷酸 DAG：二酰基甘油 二、IP3和DAG的产生和灭活 产生：PLC对PIP2的水解 PLC delta 激活移位至胞膜，PH为结合区，Cat为催化区 4，5-二磷酸磷脂酰肌醇 PIP2 磷脂酶C PLC IP3和DAG的灭活 IP2 IP3 IP4 PI3K 磷酸酶 花生四烯酸 DAG 磷脂酸 DAG激酶 磷酸酶A2 The cGMP/cGK1 system acts like an internal brake in the cardiac myocyte to suppress stress-stimulated signalling. Much of this action is thought to be mediated by cGMP-targeted kinase (cGK1) also known as protein kinase G (PKG1), which can suppress Gαq stimulation by interaction with regulator of G-protein-coupled signalling 2 (RGS2), inhibit calcium stimulation of calcineurin and RhoA, modify sarcomeric function, and influence mitochondrial function and gene transcription. cGMP synthesis is regulated by nitric oxide synthase (NOS) and by natriuretic peptides (ANP, BNP) working through two different isoforms of soluble guanylate cyclase (rGC and sGC). Available small-molecule stimulators of this process are forms of the NPs, NO-generating compounds such as isosorbide dinitrate, and direct activators of sGC (BAY 58-2776 or BAY 41-2774). cGMP can also be increased by blocking selective phosphodiesterases (PDEs) such as PDE5a (fo