Nakahara K, Yokoo H, Yoshida M, Tanaka M, Shigemori M
Department of Pharmacology, Kurume University School of Medicine, Japan.
No To Shinkei. 1994 Dec;46(12):1147-53.
Neuronal damage induced by ischemia involves various changes in neurotransmission. Nitric oxide (NO), a putative neurotransmitter and/or neuromodulator has some role in this neuronal damage. In the present study, the effect of NO on the terminal site of dopamine (DA) neurons in the rat striatum was examined using the microdialysis technique. First perfusion with sodium nitroprusside (SNP) as an NO donor increased extracellular DA (10 mM, 460%; 1 mM, 140%) in the striatum and decreased its metabolites. Pretreatment with tetrodotoxin (TTX, 5 microM), (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine hydrogen maleato (MK801, 1 microM) or muscimol (1 microM) inhibited SNP-induced increases in extracellular DA and decreases in DOPAC (TTX, complete block; MK801, 75% inhibition; muscimol, 80% inhibition). Second, extracellular NO, DA and DOPAC were measured in the gerbil striatum following 10 minutes of forebrain ischemia produced by occluding both carotid arteries. Occlusion of the carotid arteries also caused increases in extracellular NO and DA in the gerbil striatum (NO, 3000%; DA, 2800%). These findings suggest that NO-facilitated DA release occurs via interaction between glutamatergic and dopaminergic neurons. These changes are probably partially involved in the neurodegenerative phenomena following ischemia. It is also shown that simultaneous measurements of NO and DA using this technique may be useful in assessing ischemic changes in vivo.
缺血诱导的神经元损伤涉及神经传递的各种变化。一氧化氮（NO），一种假定的神经递质和/或神经调节剂，在这种神经元损伤中发挥了一定作用。在本研究中，使用微透析技术检测了NO对大鼠纹状体中多巴胺（DA）神经元终末位点的影响。首先，用硝普钠（SNP）作为NO供体进行灌注，增加了纹状体细胞外DA（10 mM时增加460%；1 mM时增加140%），并减少了其代谢产物。用河豚毒素（TTX，5 microM）、（+）-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺马来酸盐（MK801，1 microM）或蝇蕈醇（1 microM）预处理可抑制SNP诱导的细胞外DA增加和3,4-二羟基苯乙酸（DOPAC）减少（TTX，完全阻断；MK801，75%抑制；蝇蕈醇，80%抑制）。其次，在通过双侧颈总动脉闭塞造成前脑缺血10分钟后，检测沙鼠纹状体中的细胞外NO、DA和DOPAC。颈总动脉闭塞也导致沙鼠纹状体中细胞外NO和DA增加（NO，增加3000%；DA，增加2800%）。这些发现表明，NO促进的DA释放是通过谷氨酸能和多巴胺能神经元之间的相互作用发生的。这些变化可能部分参与了缺血后的神经退行性现象。还表明，使用该技术同时测量NO和DA可能有助于评估体内的缺血变化。
