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MEMBRANE DELIMITED AND INTRACELLULAR SOLUBLE PATHWAYS IN THE SOMATOSTATIN MODULATION OF ACH RELEASE

机译:膜释放和胞内可溶性途径在ACH释放的生长抑素调节中的作用

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The signal transduction cascade between the activation of the somatostatin (SOM) receptor and modulation of transmitter release was study using Acetylcholine (ACh) release measurements and patch clamp recordings of Ca2+ current from acutely dissociated St 40 ciliary ganglion neurons. As in intact synapses, somal ACh release was blocked by 100 nM SOM or 100 mu M dibutyril cGMP, and the SOM-mediated inhibition could be reversed by 10 mu M I-NAME (a selective inhibitor of nitric oxide synthase, NOS) or 100 mu M Rp-8p-CPT-cGMPs (a selective inhibitor of a cGMP protein dependent kinase, PKG). In whole cell recordings, SOM inhibition of Ca2+ current rapidly relaxes to control levels but is sustained in perforated patch recordings which decreases cell dialysis. Inhibition of NOS or PKG in perforated patch recordings, however caused SOM effects to become transient again. We hypothesize that PKG alters the characteristics of the membrane-delimited G protein inhibition of Ca2+ current. Therefore SOM receptors trigger a membrane-delimited signal transduction cascade that is modulated by soluble messengers, converging on voltage activated Ca2+ channels. When both pathways are active together, SOM causes a sustained inhibition of neuronal Ca2+ current leading to a decrease in transmitter release. [References: 18]
机译:使用乙酰胆碱(ACh)释放测量和急性解离的St 40睫状神经节神经元Ca2 +电流的膜片钳记录,研究了促生长素抑制素(SOM)受体激活与调节递质释放之间的信号转导级联。与完整的突触一样,100 nM SOM或100μM dibutyril cGMP阻止了ACh的释放,而SOM介导的抑制作用可被10μM I-NAME(一氧化氮合酶的选择性抑制剂)或100μM逆转。 μM Rp-8p-CPT-cGMPs(cGMP蛋白依赖性激酶PKG的选择性抑制剂)。在全细胞记录中,SOM对Ca2 +电流的抑制作用迅速放松至控制水平,但在穿孔的补片记录中得以维持,从而降低了细胞透析率。但是,穿孔补丁录音中NOS或PKG的抑制作用导致SOM效应再次变得短暂。我们假设PKG改变了膜定界的G蛋白抑制Ca2 +电流的特征。因此,SOM受体触发了由膜分离的信号转导级联,该信号转导由可溶性信使调节,并收敛于电压激活的Ca2 +通道上。当两个途径同时起作用时,SOM会导致神经元Ca2 +电流的持续抑制,从而导致递质释放的减少。 [参考:18]

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