The intercellular communication via nitric oxide and its regulation in coupling of cyclic GMP synthesis upon stimulation of muscarinic cholinergic receptors in rat superior cervical sympathetic ganglia
The intercellular communication via nitric oxide and its regulation in coupling of cyclic GMP synthesis upon stimulation of muscarinic cholinergic receptors in rat superior cervical sympathetic ganglia
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大鼠上交感神经节毒蕈碱胆碱能受体刺激下一氧化氮的细胞间通讯及其对环鸟苷酸合成耦合的调节
DOI：
10.1016/0006-8993(94)91793-0
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发表时间：
1994
期刊：
影响因子：
2.9
通讯作者：
Y. Nagata
中科院分区：
文献类型：
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作者：
M. Ando;T. Tatematsu;S. Kunii;Y. Nagata
大鼠上级颈交感神经节（SCG）环磷酸鸟苷（cGMP）的产生明显增加（约1.5mg/kg）。7-9倍），通过加入乙酰胆碱（ACh; 0.1 mM）或毒蕈碱激动剂卡巴胆碱（碳水化合物; 0.1 mM），在抑制剂存在下（3-异丁基-1-甲基黄嘌呤）在体外有氧孵育期间于37°C孵育5 min。ACh诱导的cGMP在SCG中的蓄积可通过进一步加入阿托品（10 μM）有效阻断（−73%），一种毒蕈碱拮抗剂，而一种烟碱阻断剂，六甲铵（10 μM）部分拮抗（−41%）这种ACh刺激。添加NG-单甲基-l-精氨酸（l-NMMA，50 μM）（一种抑制l-精氨酸合成一氧化氮（NO）的化合物）可有效增强六甲双铵对乙酰胆碱诱发的神经节cGMP产生的抑制作用（−83%）。在Carb刺激后，将fl-NMMA应用于SCG后观察到cGMP形成的相当抑制。与此相反，L-NMMA对乙酰胆碱诱发的毒蕈碱拮抗剂引起的cGMP产生水平降低没有影响。在含有血红蛋白（Hb; 20 μM）的培养基中孵育1分钟内，碳水化合物诱导的神经节cGMP合成的升高显著降低，血红蛋白是一种仅清除细胞外部分NO的试剂。此后，通过随后孵育几分钟，组织cGMP形成减弱至对照水平。在培养基中加入蛋白激酶C（PKC）激活剂12-O-十四酰基佛波醇13-乙酸酯（TPA; 1 μM）可显著降低Carb诱导的SCG cGMP合成（−61%），而超氧化物歧化酶（SOD; 30 U/ml）仅轻微抑制Carb刺激。这一发现支持了PKC可能在抑制毒蕈碱受体介导的神经节组织内NO释放增加中发挥作用的观点。在轴突切断SCG检查前一周，交感神经元变性和神经胶质细胞的反应性增殖正在进行中，没有刺激作用的碳水化合物诱导的cGMP生产通过NO释放。这些结果提供了证据表明，在交感神经元细胞中刺激毒蕈碱受体后产生的大部分NO可能在细胞外空间中自由扩散，然后被带回到相同的周围细胞群中以刺激cGMP产生。
Cyclic GMP (cGMP) production in rat superior cervical sympathetic ganglia (SCG) was markedly increased (ca. 7–9-fold) by the addition of either acetylcholine (ACh; 0.1 mM) or a muscarinic agonist, carbachol (Carb; 0.1 mM), in the presence of an inhibitor (3-isobutyl-1-methylxanthine) for cGMP hydrolytic enzyme during in vitro aerobic incubation at 37°C for 5 min. The ACh-induced accumulation of cGMP in SCG was effectively blocked (−73%) by the further addition of atropine (10 μM), a muscarinic antagonist, whereas a nicotinic blocker, hexamethonium (10 μM) partially antagonized (−41%) this ACh stimulation. The inhibitory effect of hexamethonium on ACh-evoked ganglionic cGMP production was effectively augmented (−83%) by addition ofNG-monomethyl-l-arginine, (l-NMMA, 50 μM), a compound that inhibits nitric oxide (NO) synthesis froml-arginine. Comparable inhibition of cGMP formation was observed following application ofl-NMMA to the SCG upon stimulation of Carb. In contrast,l-NMMA had no effect on the decreased level of ACh-evoked cGMP production caused by the muscarinic antagonist. The Carb-induced elevation of ganglionic cGMP synthesis was significantly reduced within 1 min of incubation in the medium containing hemoglobin (Hb; 20 μM), an agent that scavenges only the extracellular fraction of NO. Thereafter, the tissue cGMP formation attenuated to the control level by subsequent incubation for several minutes. Addition of protein kinase C (PKC) activator,12-O-tetradecanoylphorbol 13-acetate (TPA; 1 μM) to the medium significantly decreased Carb-evoked cGMP synthesis (−61%) in SCG, whereas superoxide dismutase (SOD; 30 U/ml) only slightly suppressed the Carb stimulation. This finding supports the idea that PKC might play a role in dampening the muscarinic receptor-mediated increase in NO release within ganglionic tissue. In axotomized SCG one week prior to examination, where sympathetic neurons were degenerated and reactive proliferation of glial cells was in progress, no stimulatory effect of Carb-induced cGMP production via NO release was seen. These results provide evidence that a large fraction of NO generated upon stimulation of muscarinic receptors in sympathetic neuronal cells can possibly freely diffuse in extracellular space, and then be taken back into the same group of surrounding cells to stimulate cGMP production.
DOI：
--
发表时间：
1985-03
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
W. Martin;G. Villani;D. Jothianandan;R. Furchgott
通讯作者：
W. Martin;G. Villani;D. Jothianandan;R. Furchgott