2015-10-27 神经递质与受体.ppt

Second messenger systems The G protein activates a second messenger which then activates any number of other mechanisms inside the cell, which can alter the intracellular calcium concentration, open/close channels, alter gene production 胞浆内第二信使(Second Messengers) 细胞外信使物质称第一信使,包括经典的神经递质、神经肽、多肽激素和细胞因子(如白细胞介素和生长因子)等. 第一信使作用于靶细胞后刺激胞浆内产生的信息分子称第二信使，是细胞外信息与细胞内效应之间必不可少的中介物,包括： 环核苷酸类(cAMP, cGMP) 细胞膜肌醇磷脂代谢产物(三磷酸肌醇IP3,甘油二酯DAG) Ca2+ No 花生四烯酸的代谢产物 另一类负责细胞核内外信息传递的物质称第三信使,包括生长因子、转化因子及其受体、转导蛋白及某些癌基因产物，参与基因调控、细胞增殖和分化等过程。 cAMP “腺苷-3’,5’-环化一磷酸”的简称, 是第一个被发现的第二信使。 cAMP与肿瘤有一定的关系，正常细胞和肿瘤细胞中的cAMP含量是有差异的，在肿瘤细胞内cAMP一般低于正常细胞水平。 蛋白激酶A(Protein Kinase A, PKA)：cAMP依赖性蛋白激酶 蛋白激酶G(Protein Kinase G、PKG) ：cGMP依赖性蛋白激酶 蛋白激酶C(Protein Kinase C、PKC)：磷脂酰肌醇的衍生物如DAG、PIP3(三磷酸磷脂酰肌醇)、磷脂酰胆碱的衍生物、鞘磷脂的衍生物以及Ca2＋依赖性蛋白激酶。 cAMP激活PKA G-蛋白偶联的第二信使级联的信号经放大 Glutamate neurotransmission Synthesis, packaging, reuptake, degradation (error - should be EAAT) Molecular diversity of glutamate receptors: 3 types, based on sensitivity to pharmacological agents: AMPA, kainate, N-methyl d-aspartate (NMDA) AMPA: homotetramers or heterotetramers assembled from Glu R1-4 subunits NMDA: heterotetramers that contain an NR1 subunit, and a subunit from the NR2 family Kainate: heterotetramers containing subunits from the KA1,2 family, and from the GluR5-7 family AMPA receptor structure (NMDA, kainate receptors have the same principal structural features) Also called GluR-1 through 4 Expression patterns of AMPA receptor subunits in the brain AMPA receptor functional diversity Mixing and matching of subunits (see GABA receptors for examples) Further diversity generated by alternative splicing, editing Flip and flop splice forms desensitize at different rates, both have rapid onset kinetics (gluR2 homomers shown) Kandel, Schwartz, Jessel (2000) Principles of Neural Science 4ed Ion selectivity is modulated by RNA editing NMDA receptors NMDA receptors show slow onset and decay kinetics Some synapses have both glutamate receptor ty