Agopyan N, Krnjević K
Department of Physiology, McGill University, Montréal, Qué., Canada.
Brain Res. 1990 Aug 20;525(2):294-9. doi: 10.1016/0006-8993(90)90877-e.
It has been proposed that, in a variety of tissues, guanosine 3':5'-monophosphate (cyclic GMP) is the intracellular mediator of muscarinic effects. This hypothesis was tested in the CA1 region of the hippocampus, in urethane-anaesthetized rats, by studying extracellularly muscarinic disinhibition of disfacilitation and the effect of dibutyryl cyclic GMP, muscarinic agents and an inhibitor of cyclic nucleotide-dependent kinase (H-8), all applied by microiontophoresis. The main findings were: (a) cyclic GMP analogues do not mimic disfacilitation or disinhibition produced by muscarinic agents; (b) N-(2-(methylamino)ethyl)-5-isoquinoline sulfonamide (H-8) does not prevent the excitatory actions of muscarinic agents; and (c) H-8 alone does not change the field responses. In conclusion, cyclic nucleotide-dependent kinases do not seem to play a major role in the on-going modulation of excitability in the hippocampus and cyclic GMP is unlikely to be a major intracellular messenger mediating directly or indirectly the excitatory actions of acetylcholine.
有人提出，在多种组织中，鸟苷3':5'-单磷酸（环磷酸鸟苷）是毒蕈碱效应的细胞内介质。在氨基甲酸乙酯麻醉的大鼠海马CA1区，通过细胞外研究毒蕈碱对易化抑制的去抑制作用以及二丁酰环磷酸鸟苷、毒蕈碱剂和环核苷酸依赖性激酶抑制剂（H-8）的作用（均通过微离子电泳施加），对这一假说进行了检验。主要发现如下：（a）环磷酸鸟苷类似物不能模拟毒蕈碱剂产生的易化抑制或去抑制作用；（b）N-(2-(甲氨基)乙基)-5-异喹啉磺酰胺（H-8）不能阻止毒蕈碱剂的兴奋作用；（c）单独使用H-8不会改变场反应。总之，环核苷酸依赖性激酶似乎在海马兴奋性的持续调节中不起主要作用，环磷酸鸟苷不太可能是直接或间接介导乙酰胆碱兴奋作用的主要细胞内信使。
