Bianchi C, Tomasini M C, Antonelli T, Marani L, Beani L
Department of Clinical and Experimental Medicine, Pharmacology Section, University of Ferrara, Italy.
Synapse. 2000 Jun 15;36(4):307-13. doi: 10.1002/(SICI)1098-2396(20000615)36:4<307::AID-SYN7>3.0.CO;2-P.
The effect of nicotine on basal and electrically evoked (20 Hz for 20 sec) [(3)H]D-aspartate efflux (assumed as an index of transmitter release) was studied in rat cerebellar granule primary cultures. Nicotine (10-100 nM) increased the basal efflux two to three times and concentration-dependently enhanced the electrically evoked efflux up to ten times. Higher drug concentration (1 microM) underwent rapid desensitization. Facilitation of the efflux was similarly reduced by the nicotinic acetylcholine receptor antagonists, alpha-bungarotoxin and mecamylamine, suggesting the involvement of at least two receptor subtypes containing and lacking alpha(7) subunits, respectively. Since the increased efflux induced by nicotine in granule cells kept at rest or depolarized by KCl 15 mM was antagonized by tetrodotoxin, the involvement of sodium channels by receptors located at preterminal sites was suggested. Taken together, these findings emphasize the role of the cholinergic input in granule cell function and in glutamatergic signaling.
在大鼠小脑颗粒原代培养物中，研究了尼古丁对基础和电诱发（20Hz，持续20秒）的[（3）H]D-天冬氨酸外流（假定为递质释放指标）的影响。尼古丁（10 - 100 nM）使基础外流增加两到三倍，并浓度依赖性地将电诱发外流增强至十倍。更高的药物浓度（1μM）会迅速脱敏。烟碱型乙酰胆碱受体拮抗剂α-银环蛇毒素和美加明同样降低了外流的促进作用，这表明至少分别涉及两种含有和缺乏α（7）亚基的受体亚型。由于在静息状态或由15 mM KCl去极化的颗粒细胞中，尼古丁诱导的外流增加被河豚毒素拮抗，提示位于突触前位点的受体参与了钠通道的作用。综上所述，这些发现强调了胆碱能输入在颗粒细胞功能和谷氨酸能信号传导中的作用。
