Zhuo M, Hu Y, Schultz C, Kandel E R, Hawkins R D
Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, New York.
Nature. 1994 Apr 14;368(6472):635-9. doi: 10.1038/368635a0.
Several lines of evidence suggest that cyclic GMP might be involved in long-term potentiation (LTP) in the hippocampus. Arachidonic acid, nitric oxide and carbon monoxide, three molecules that have been proposed to act as retrograde messengers in LTP, all activate soluble guanylyl cyclase. We report here that an inhibitor of guanylyl cyclase blocks the induction of LTP in the CA1 region of hippocampal slices. Conversely, cGMP analogues produce long-lasting enhancement of the excitatory postsynaptic potential if they are applied at the same time as weak tetanic stimulation of the presynaptic fibres. The enhancement is spatially restricted, is not blocked by valeric acid (APV), nifedipine, or picrotoxin, and partially occludes LTP. This synaptic enhancement may be mediated by the cGMP-dependent protein kinase (PKG). Inhibitors of PKG block the induction of LTP, and activators of PKG produce activity-dependent long-lasting enhancement. These results suggest that guanylyl cyclase and PKG contribute to LTP, possibly as activity-dependent presynaptic effectors of retrograde messengers.
多项证据表明，环磷酸鸟苷（cGMP）可能参与海马体中的长时程增强（LTP）。花生四烯酸、一氧化氮和一氧化碳这三种分子被认为在LTP中充当逆行信使，它们均能激活可溶性鸟苷酸环化酶。我们在此报告，鸟苷酸环化酶抑制剂可阻断海马体切片CA1区LTP的诱导。相反，如果在对突触前纤维进行弱强直刺激的同时应用cGMP类似物，它们会使兴奋性突触后电位产生持久增强。这种增强在空间上受到限制，不受戊酸（APV）、硝苯地平或苦味毒的阻断，并且部分阻断LTP。这种突触增强可能由cGMP依赖性蛋白激酶（PKG）介导。PKG抑制剂可阻断LTP的诱导，而PKG激活剂则产生依赖于活动的持久增强。这些结果表明，鸟苷酸环化酶和PKG对LTP有贡献，可能作为逆行信使的依赖于活动的突触前效应器。
