REGULATION OF BRAIN NICOTINIC RECEPTORS BY CHRONIC AGONIST INFUSION
REGULATION OF BRAIN NICOTINIC RECEPTORS BY CHRONIC AGONIST INFUSION
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DOI：
10.1111/j.1471-4159.1991.tb03450.x
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发表时间：
1991-06-01
影响因子：
4.7
通讯作者：
COLLINS, AC
中科院分区：
文献类型：
--
作者：
BHAT, RV;TURNER, SL;COLLINS, AC
几项研究表明，长期服用尼古丁会增加大脑中尼古丁受体的数量。为了确定这种效应是否被烟草中发现的其他尼古丁激动剂所引起，我们比较了长期注射尼古丁对大脑尼古丁受体的影响，并与阿纳巴辛和洛贝林进行了比较。C57BL/6小鼠分别给予生理盐水或等摩尔剂量(18.5mU·mol/kg/h)的尼古丁、阿纳巴辛或洛贝林灌胃8天。然后用[H-3]尼古丁和[I-125]碘-银环蛇毒素(α-[I-125]BTX)结合的尼古丁受体和[H-3]奎宁苯甲酸酯([H-3]QNB)的结合定量的毒碱受体在8个脑区进行了测定。除小脑外，所有区域的[H-3]尼古丁结合量均增加，但洛贝林不改变这些结合点的数目或亲和力。这种增加是由于B(Max)的变化，而不是配体受体亲和力(K(D))的变化。皮质区α-[I-125]BTX结合量在慢性注射阿那巴辛后略有增加。[H-3]QNB结合位点在长期注入任何尼古丁类似物后基本没有改变。慢性治疗后还测定了脑组织中激动剂的水平，发现洛贝林和阿纳巴辛的含量高于尼古丁。因此，洛贝林未能引起尼古丁结合的变化并不是由于大脑浓度降低所致。
Several studies have demonstrated that chronic treatment with nicotine elicits an increase in the number of brain nicotinic receptors. To determine whether this effect is elicited by other nicotinic agonists found in tobacco, the effects of chronic infusion with nicotine on brain nicotinic receptors were compared with those after anabasine and lobeline. C57BL/6 mice were infused with saline or equimolar doses (18.5-mu-mol/kg/h) of nicotine, anabasine, or lobeline for 8 days. Nicotinic receptors, quantified by the binding of [H-3]nicotine and [I-125]iodo-alpha-bungarotoxin (alpha-[I-125]BTX), and muscarinic receptors, quantified by the binding of [H-3]quinuclidinyl benzilate ([H-3]QNB), were then assayed in eight brain regions. An increase in [H-3]nicotine binding was observed in all regions except cerebellum following chronic infusion with nicotine and anabasine, whereas lobeline did not alter the number or affinity of these binding sites. This increase was due to changes in B(max) and not in the affinity of the receptor for the ligand (K(D)). A slight increase in alpha-[I-125]BTX binding was observed in cortex following chronic anabasine infusion. [H-3]QNB binding sites were largely unaltered following chronic infusion with any of the nicotinic analogs. The levels of the agonists in the brain were also determined after chronic treatment, and the amounts of lobeline and anabasine were found to be higher than that of nicotine. Thus, the failure of lobeline to elicit changes in nicotine binding is not due to reduced brain concentrations.