Nitric oxide from the laterodorsal tegmental neurons: Its possible retrograde modulation on norepinephrine release from the axon terminal of the locus coeruleus neurons
Nitric oxide from the laterodorsal tegmental neurons: Its possible retrograde modulation on norepinephrine release from the axon terminal of the locus coeruleus neurons
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DOI：
10.1016/j.neuroscience.2005.10.063
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Koyama, Y
中科院分区：
文献类型：
--
作者：
Kodama, T;Koyama, Y
脑桥胆碱能神经元释放的一氧化氮可能在睡眠-觉醒调节中起重要作用。然而，关于脑桥胆碱能神经元释放一氧化氮的机制的报道很少。本研究采用在体微透析技术研究了N-甲基-D-天冬氨酸给药对大鼠中脑被盖背外侧核（LDT）一氧化氮和神经递质释放的影响，以阐明一氧化氮在胆碱能系统中的作用。在LDT中加入1 mM的N-甲基-D-天冬氨酸（N-methyl-D-asparticacid，N-methyl-D-asparticacid，N-methyl-D-asparticacid）40 min后，NO_2和NO_3浓度显著升高（P < 0.001）。同样剂量的N-甲基-D-天冬氨酸可使环鸟苷酸（cGMP）在30 min时显著升高（P < 0.05），乙酰胆碱（P < 0.001）和去甲肾上腺素（P < 0.001）在15 min时显著升高（P < 0.001）。3-（4-Morpholinyl）-sydonone imine hydrochloride（一氧化氮供体，5 mM）也诱导去甲肾上腺素的显著增加（P < 0.05）。用1 mM 2-氨基-5-膦酰基戊酸预处理（N-甲基-D-天冬氨酸受体拮抗剂）阻止了N-甲基-D-天冬氨酸诱导的环鸟苷酸增加（P < 0.01）、乙酰胆碱和去甲肾上腺素（P < 0.01），而1 mM N-G-硝基-L-精氨酸一氧化氮合酶抑制剂可抑制环鸟苷酸（P < 0.01）和去甲肾上腺素（P < 0.01）的升高，但对乙酰胆碱无影响。这些结果表明，LDT胆碱能神经元上的N-甲基-D-天冬氨酸受体被激活，从而引起LDT内NO的释放，进而通过cGMP系统促进蓝斑去甲肾上腺素能神经元末梢释放去甲肾上腺素。基于这些发现，我们提出一氧化氮在LDT中的可能作用是作为蓝斑去甲肾上腺素释放的逆行调节剂。(c)2005由Elsevier Ltd代表IBRO出版。
Nitric oxide released from the cholinergic neurons in the pons may play important roles in sleep-wake regulation. However, there are few reports demonstrating the mechanisms of nitric oxide release in the cholinergic neurons in the pons. The present study investigated the effects of drug delivery of N-methyl-D-aspartic acid on nitric oxide and the neurotransmitters released in the laterodorsal tegmental nucleus (LDT), one of the major cholinergic cell groups in the pons, in rats by in vivo microdialysis with a view to clarifying nitric oxide functions in the cholinergic system. The application of N-methyl-D-aspartic acid (1 mM) into the LDT induced a significant increase in NO2 and NO3 for 40 min (P < 0.001). Furthermore the same dose of N-methyl-D-aspartic acid induced a significant increase in cyclic GMP for 30 min (P < 0.05), as well as in acetylcholine (P < 0.001) and norepinephrine for 15 min (P < 0.001). 3-(4-Morpholinyl)-sydonone imine hydrochloride (a nitric oxide donor, 5 mM) also induced significant increase in norepinephrine (P < 0.05). Pretreatment with 1 mM 2-amino-5-phosphonopentanoic acid (an antagonist of N-methyl-D-aspartic acid receptor) prevented the N-methyl-D-aspartic acid-induced increase in cyclic GMP (P < 0.01), acetylcholine and norepinephrine (P < 0.01), while that with 1 mM N-G-nitro-L-arginine (an inhibitor of nitric oxide synthase) prevented the increase in cyclic GMP (P < 0.01) and norepinephrine (P < 0.01) but not in acetylcholine. These results suggested that nitric oxide release in the LDT induced by activation of the N-methyl-D-aspartic acid receptor on the cholinergic neurons of the LDT, then through the cyclic GMP system, facilitates norepinephrine release from the terminals of noradrenergic neurons in the locus coeruleus. Based on these findings, we propose a possible role of nitric oxide in the LDT is as a retrograde regulator of norepinephrine release from the locus coeruleus. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.