Nitric oxide-induced adenosine inhibition of hippocampal synaptic transmission depends on adenosine kinase inhibition and is cyclic GMP independent
Nitric oxide-induced adenosine inhibition of hippocampal synaptic transmission depends on adenosine kinase inhibition and is cyclic GMP independent
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DOI：
10.1111/j.1460-9568.2006.05124.x
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发表时间：
2006-11-01
影响因子：
3.4
通讯作者：
Rosenberg, Paul A.
中科院分区：
文献类型：
--
作者：
Arrigoni, Elda;Rosenberg, Paul A.
腺苷是一种重要的抑制性神经调质，调节神经元兴奋性。一些研究表明，一氧化氮诱导腺苷的释放。在这里，我们研究了这种释放的机制。本研究观察了一氧化氮对大鼠海马脑片CA 1区诱发场兴奋性突触后电位（fEPSPs）的影响。一氧化氮供体1，1-二乙基-2-羟基-2-亚硝基肼钠（DEA/NO; 100 μ M）使fEPSP降低77.6 +/-4.1%。这种作用被腺苷A1拮抗剂8-环戊基-1，3-二丙基黄嘌呤（DPCPX; 400 nM）消除，表明一氧化氮的作用是由腺苷积累介导的。DEA/NO效应不受5 ′-外核苷酸酶抑制剂α，β-亚甲基腺苷5 ′-二磷酸（AMP-CP; 100 μ M）的影响，表明细胞外腺苷不是来自ATP或cAMP释放。鸟苷酸环化酶抑制剂1H-[1，2，4]恶二唑[4，3-a]喹喔啉-1-酮（ODQ; 5 μ M）不影响fEPSP的一氧化氮抑制，表明一氧化氮介导的腺苷释放不是通过cGMP信号级联介导的。这一结论通过观察到8-（4-氯苯硫基）-鸟苷-3 '，5'-环一磷酸（8-pCPT-cGMP; 1 mM）可逆地抑制fEPSP 24.9 +/-4.5%而得到证实，但这种作用不被腺苷拮抗剂阻断。腺苷激酶抑制剂5-iodotubercidin（ITU; 7 μ M）闭塞了74%的一氧化氮的影响，这表明腺苷激酶活性的抑制有助于腺苷的释放。总之，外源性一氧化氮通过cGMP非依赖性途径引起腺苷释放。细胞内cGMP升高部分抑制fEPSP，但不是通过腺苷释放。虽然不能排除一氧化氮对腺苷激酶的直接阻断，但腺苷激酶活性的抑制可能是由于其自身底物腺苷的抑制。
Adenosine is an important inhibitory neuromodulator that regulates neuronal excitability. Several studies have shown that nitric oxide induces release of adenosine. Here we investigated the mechanism of this release. We studied the effects of nitric oxide on evoked field excitatory postsynaptic potentials (fEPSPs) recorded in the CA1 area of rat hippocampal slices. The nitric oxide donor 1,1-diethyl-2-hydroxy-2-nitroso-hydrazine sodium (DEA/NO; 100 mu M) depressed the fEPSP by 77.6 +/- 4.1%. This effect was abolished by the adenosine A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 400 nM), indicating that the nitric oxide effect was mediated by adenosine accumulation. The DEA/NO effect was unaltered by the 5'-ectonucleotidase inhibitor alpha,beta-methylene-adenosine 5'-diphosphate (AMP-CP; 100 mu M), indicating that extracellular adenosine did not derive from ATP or cAMP release. The guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxaline-1-one (ODQ; 5 mu M) did not affect nitric oxide depression of the fEPSPs, indicating that nitric oxide-mediated adenosine release was not mediated through a cGMP signaling cascade. This conclusion was confirmed by the observation that 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP; 1 mM) reversibly depressed the fEPSP by 24.9 +/- 4.5%, but this effect was not blocked by adenosine antagonists. Adenosine kinase inhibitor 5-iodotubercidin (ITU; 7 mu M) occluded the nitric oxide effects by 74%, suggesting that inhibition of adenosine kinase activity contributes to adenosine release. In conclusion, exogenous nitric oxide evokes adenosine release by a cGMP-independent pathway. Intracellular cGMP elevation partially inhibits the fEPSP but not through adenosine release. Although a direct block of adenosine kinase by nitric oxide can not be excluded, the depression of adenosine kinase activity may be due to inhibition by its own substrate adenosine.