胍丁胺对大鼠穹隆下器神经元电活动的影响(英文)

Effects of agmatine on the electrical activity of subfornical organ neurons

应用细胞外记录单位放电技术,在73个大鼠穹隆下器脑片上观察了胍丁胺(agmatine,Agm)对神经元电活动的影响。实验结果如下:(1)在28个穹隆下器脑片上灌流Agm(1.0 μmol/L)2 min,有24个单位(85.7％)自发放电频率明显降低,4个单位(14.3%)无明显变化;(2)预先用L-谷氨酸(0-3 mmol/L)灌流,24个放电单位中有19个单位(79.2％)放电频率明显增加,表现为癫痫样放电,5个单位(20.8％)的变化不明显,在此基础上灌流Agm(1.0 μmol/L)2 min,有15个单位(78.9％)的癫痫样放电被抑制,另外4个单位(21.1％)无明显变化;(3)灌流L型钙通道激动剂Bay K-8644(0.1 μmol/L),在12个神经元放电单位中有10个单位(83.3%)的放电频率明显增加,另外2个单位(16.7％)变化不明显,然后灌流Agm(1.0 μmol/L)2 min,有8个单位(80％)的放电频率被抑制,其余无明显变化;(4)9个单位在灌流一氧化氮合酶(NOS)抑制剂NG-nitro-L-arginine-methyl estel(L-NAME,50μmol/L)后,其中6个单位(66.7％)放电频率明显增加,另外3个单位(33.3％)放电频率变化不明显,在此基础上再给予Agm(1.0μmol/L)2 min,增加的放电频率被抑制。上述结果提示:胍丁胺可抑制大鼠穹隆下器神经元自发放电以及由L-谷氨酸,Bay K-8644和L-NAME诱发的放电。

The aim of this study was to investigate the effects of agmatine (Agm) on the electrical activity of neurons in subfornical organ (SFO) slices using extracellular recording technique. The results are as follows. (1) In response to the application of Agm (1.0 μmol/L) into the superfusate for 2 min, the discharge rate of 24/28 (85.7%) subfornical neurons was decreased significantly, while the discharge rate of 4/28 (14. 3%) neurons were not affected. (2) Pretreatment with L-glutamate (0.3 mmol/L) led to a marked increase in the discharge rate of 19/24 (79.2%) subfornical neurons in an epileptiform pattern and the activity of the remaining 5/24 (20.8%) neurons was unaffected. By application of Agm (1.0 μmol/L) into the superfusate for 2 min, the epileptiform dicharge of 15/19 (78.9%) neurons was suppressed significantly, while that of the other 4 (21.1%) neurons was not inhibited. (3) In 12 neurons, perfusion of the selective L-type calcium channel agonist, Bay K-8644 (0.1 μmol/L), induced a significant increase in the discharge rate of 10/12 (83.3%) neurons, while the other 2 (16.7%) neurons showed no change. The increased discharge of 8/10 (80%) neurons was reduced by application of Agm (1.0 μmol/L) into the superfusate and that of 2/10 (20%) neurons was not affected. (4) Application of nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 50 μmol/L) into the superfusate also significantly increased the discharge rate of 6/9 (66.7%) neurons, and that of 3/9 (33.3%) neurons had no response. Agm (1.0 μmol/L) applied into the superfusate reduced the increased discharge of all 6/6 (100%) neurons. These results suggest that Agm can inhibit the spontaneous discharge, and L-glutamate, Bay K-8644- or L-NAME-induced discharge of neurons in SFO. These inhibitory effects of Agm may be related to the blockade of NMDA receptors and reduction in calcium influx in SFO neurons.