Toth E
Nathan S. Kline Institute for Psychiatric Research, Center for Neurochemistry, Orangeburg, New York 10962, USA.
Neurochem Res. 1996 Aug;21(8):903-7. doi: 10.1007/BF02532339.
Using microdialysis, we compared intracerebral and subcutaneous administration of nicotine for the effect on the levels of extracellular amino acids in the hippocampus of anesthetized rats. Administration by microdialysis of 10 mM nicotine, resulting in a nicotine concentration of 0.134 mumol/g in the hippocampus, increased the extracellular levels of aspartic acid, glutamic acid, and serine by 26-60%. At 50 mM nicotine the increases in the levels of aspartic acid, glutamic acid, serine, glycine, and glutamine were between 76% and 141%. Subcutaneous administration of nicotine at a dose of 6 mumol/kg caused a 57% increase in the extracellular level of glutamic acid. After a dose of 12 mumol/kg that resulted in a nicotine level of 0.015 mumol/kg in the hippocampus, the extracellular level of glutamic acid was increased by 100%, and that of aspartic acid by 24%. Thus, higher cerebral nicotine levels were needed with intracerebral than with subcutaneous administration to obtain similar amino acid changes. Prior administration of mecamylamine or L-kynurenine prevented the subcutaneous nicotine-induced elevation of the extracellular levels of aspartic acid and glutamic acid. Our results indicate that receptor interactions modulate nicotine effects and that both nicotinic cholinergic and NMDA/glycine glutamatergic receptors participate in the action of nicotine in increasing extracellular amino acid levels.
我们使用微透析技术，比较了向麻醉大鼠海马体中脑内和皮下注射尼古丁对细胞外氨基酸水平的影响。通过微透析注射10 mM尼古丁，使海马体中的尼古丁浓度达到0.134 μmol/g，可使天冬氨酸、谷氨酸和丝氨酸的细胞外水平提高26%至60%。在注射50 mM尼古丁时，天冬氨酸、谷氨酸、丝氨酸、甘氨酸和谷氨酰胺水平的升高幅度在76%至141%之间。皮下注射6 μmol/kg的尼古丁可使谷氨酸的细胞外水平升高57%。在注射12 μmol/kg剂量的尼古丁后，海马体中的尼古丁水平达到0.015 μmol/kg，谷氨酸的细胞外水平升高了100%，天冬氨酸升高了24%。因此，与皮下注射相比，脑内注射需要更高的尼古丁水平才能获得相似的氨基酸变化。预先注射美加明或L-犬尿氨酸可阻止皮下注射尼古丁引起的天冬氨酸和谷氨酸细胞外水平升高。我们的结果表明，受体相互作用调节尼古丁的作用，并且烟碱型胆碱能受体和NMDA/甘氨酸谷氨酸能受体均参与尼古丁升高细胞外氨基酸水平的作用。
