Subsets of acetylcholine-stimulated 86Rb+ efflux and [125I]-epibatidine binding sites in C57BL/6 mouse brain are differentially affected by chronic nicotine treatment
Subsets of acetylcholine-stimulated 86Rb+ efflux and [125I]-epibatidine binding sites in C57BL/6 mouse brain are differentially affected by chronic nicotine treatment
复制标题
DOI：
10.1016/j.neuropharm.2004.02.009
复制
发表时间：
2004-06-01
影响因子：
4.7
通讯作者：
Collins, AC
中科院分区：
文献类型：
--
作者：
Marks, MJ;Rowell, PP;Collins, AC
长期尼古丁治疗后，以高亲和力结合尼古丁的烟碱胆碱能受体 (nAChR) 位点（可能是 alpha4beta2-nAChR）增加。慢性治疗油对其他 nAChR 结合位点的影响以及 nAChR 的功能反应研究较少。因此，C57BL/6小鼠静脉注射生理盐水或尼古丁（5剂，0.25-4.0mg/kg/h）10天，评估nAChR功能，并评估12个脑区的3个不同的烟碱结合位点。血浆尼古丁和可替宁呈线性增加，接近。对乙酰胆碱敏感性较高的Rb-86(+)流出量随着剂量的增加而趋于减少，而对乙酰胆碱敏感性较低的Rb-86(+)流出量则趋于增加。正如预期的那样，可能的 alpha4beta2-nAChR [I-125]-epibatidine 结合位点随着治疗而增加（最大增加一半的估计剂量为 0.44 mg/kg/h，血浆尼古丁大约为 20 ng/ml）对乙酰胆碱和金雀花氨酸敏感的 [I-125]-epibatidine 结合具有更高敏感性的 Rb-86(+) 外流主要是α4β2-nAChR。在整个大脑区域中观察到这些参数之间存在高度相关性，并且这些回归线的斜率随着治疗的接近而降低，表明每单位受体的功能下降。即使在最高剂量（4.0 mg/kg/h，大约 210 ng/ml）下，α3β4-nAChR 结合位点可能也不受影响。第三组不同的 nAChR 结合位点在某些大脑区域有所增加，但仅在高强度治疗后才出现。 (C) 2004 Elsevier Ltd. 保留所有权利。
Nicotinic cholinergic receptor (nAChR) sites that bind nicotine with high affinity (likely alpha4beta2-nAChR) increase following chronic nicotine treatment. Effects of Chronic treatment oil other nAChR binding sites and functional responses of nAChRs are less well studied. Therefore, C57BL/6 mice were intravenously infused for 10 days with saline or nicotine (five doses, 0.25 4.0 mg/kg/h) and nAChR function and three different nicotinic binding sites in 12 brain regions were assessed. Plasma nicotine and cotinine increased linearly with close. Rb-86(+) efflux with higher sensitivity to acetylcholine tended to decrease with increasing dose, whereas efflux with lower sensitivity to acetylcholine tended to increase. As anticipated likely alpha4beta2-nAChR [I-125]-epibatidine binding sites increased with treatment (estimated dosage for one-half maximal increase was 0.44 mg/kg/h, plasma nicotine approximate to20 ng/ml) Rb-86(+) efflux with higher sensitivity to acetylcholine and cytisine-sensitive [I-125]-epibatidine binding are predominantly alpha4beta2-nAChR. A high correlation between these parameters was observed across brain regions and slopes of these regression lines decreased with treatment close, suggesting a decrease in function per unit receptor. Likely alpha3beta4-nAChR binding sites were unaffected even at the highest dose (4.0 mg/kg/h, approximate to210 ng/ml). A third set of diverse nAChR binding sites increased in some brain regions, but only after high-close treatment. (C) 2004 Elsevier Ltd. All rights reserved.