Köfalvi A, Sperlágh B, Zelles T, Vizi E S
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
J Pharmacol Exp Ther. 2000 Nov;295(2):453-62.
In this study we explored the effect of the stimulation of nicotinic acetylcholine receptors located on interneurons by measuring 4-amino-n-[2,3-(3)H]butyric acid ([(3)H]GABA) release and monitoring Ca (2+) in superfused hippocampal slices. In the presence of 6-cyano-7-nitroquinoxaline-2,3-dione, (+/-)-2-amino-5-phosphonopentanoic acid, and atropine, i.e., under the blockade of N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate and muscarinic receptors, nicotine did not alter the spontaneous outflow of [(3)H]GABA, but significantly increased the stimulation-evoked [(3)H]GABA efflux. This effect of nicotine depended on the time interval between nicotine treatment and electrical stimulus, the concentration of nicotine (1-100 microM), and the parameters of electrical depolarization. Acetylcholine (0.03-3 mM), and the alpha 7 subtype-selective agonist choline (0.1-10 mM), also potentiated stimulus-evoked release of [(3)H]GABA, whereas 1,1-dimethyl-4-phenilpiperazinium iodide failed to increase the tritium outflow significantly. The effect of nicotine treatment was prevented by tetrodotoxin (1 microM) and by the nicotinic acetylcholine receptor antagonist mecamylamine (10 microM), and the alpha 7 subtype-selective antagonists alpha-bungarotoxin (100 nM) and methyllycaconitine (10 nM), whereas dihidro-beta-erythroidine (20 nM) was without effect. Perfusion of 100 microM nicotine caused a Ca(2+) transient in about one-third of the tested interneurons; however, the response to subsequent electrical stimulation remained unchanged. Inhibition of the GABA transporter system by nipecotic acid (1 mM) or by decreasing the bath temperature to 12 degrees C abolished completely the effect of nicotine to potentiate the stimulation-evoked release of GABA. These findings indicate that the activation of alpha 7-type nicotinic receptors of hippocampal interneurons results in a long-lasting ability of these cells to respond to depolarization with an increased release of GABA mediated by the transporter system.
在本研究中，我们通过测量4-氨基-n-[2,3-(3)H]丁酸（[(3)H]GABA）释放并监测灌流海马脑片中的Ca (2+)，探究了对中间神经元上烟碱型乙酰胆碱受体的刺激作用。在存在6-氰基-7-硝基喹喔啉-2,3-二酮、(+/-)-2-氨基-5-膦酰基戊酸和阿托品的情况下，即N-甲基-D-天冬氨酸和非N-甲基-D-天冬氨酸谷氨酸受体以及毒蕈碱受体被阻断时，尼古丁不会改变[(3)H]GABA的自发外流，但会显著增加刺激诱发的[(3)H]GABA外流。尼古丁的这种作用取决于尼古丁处理与电刺激之间的时间间隔、尼古丁的浓度（1-100 microM）以及电去极化参数。乙酰胆碱（0.03-3 mM）和α7亚型选择性激动剂胆碱（0.1-10 mM）也增强了刺激诱发的[(3)H]GABA释放，而碘化1,1-二甲基-4-苯基哌嗪未能显著增加氚外流。尼古丁处理的作用可被河豚毒素（1 microM）以及烟碱型乙酰胆碱受体拮抗剂美加明（10 microM）、α7亚型选择性拮抗剂α-银环蛇毒素（100 nM）和甲基lycaconitine（10 nM）阻断，而二氢-β-刺桐啶（20 nM）则无作用。灌注100 microM尼古丁会在约三分之一的受试中间神经元中引起Ca(2+)瞬变；然而，对随后电刺激的反应保持不变。用尼克酸（烟碱酸，1 mM）抑制GABA转运系统或降低浴温至12摄氏度可完全消除尼古丁增强刺激诱发的GABA释放的作用。这些发现表明，海马中间神经元α7型烟碱受体的激活导致这些细胞具有持久的能力，能够通过转运系统介导的GABA释放增加来对去极化作出反应。
