Chronic nicotine administration does not increase nicotinic receptors labeled by [125 I]epibatidine in adrenal gland, superior cervical ganglia, pineal or retina
Chronic nicotine administration does not increase nicotinic receptors labeled by [125 I]epibatidine in adrenal gland, superior cervical ganglia, pineal or retina
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DOI：
10.1046/j.1471-4159.2003.01774.x
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发表时间：
2003-06-01
影响因子：
4.7
通讯作者：
Kellar, KJ
中科院分区：
文献类型：
--
作者：
Dávila-García, MI;Musachio, JL;Kellar, KJ
通过渗透泵连续暴露于生理盐水或酒石酸氢尼古丁（3.3或10 mg/kg/天）14天后，测定CNS和外周组织中的神经元烟碱乙酰胆碱受体（nAChR）。首先，比较[（3）H]（-）尼古丁、[（3）H]野靛碱和[（3）H]地棘蛙素与nAChR的结合，以确定每种方法对这些研究的适用性。在大脑皮层中，激动剂标记的主要nAChR是α 4 β 2亚型，而肾上腺、上级颈神经节和松果体中的主要烟碱受体含有α 3亚基，并且它们不以高亲和力结合[（3）H]（-）尼古丁或[（3）H]金雀花碱。在视网膜中，一些nAChR以高亲和力结合所有三种配体，而另一些似乎仅结合[（3）H]地棘蛙素。因此，只有[（3）H]地棘蛙素具有足够高的亲和力，可用于测量所有组织中的nAChR。然后使用[（125）I]地棘蛙素测量尼古丁处理大鼠的受体，其结合特性与[（3）H]地棘蛙素非常相似。两种剂量的尼古丁酒石酸氢盐治疗分别使大脑皮层中的结合位点增加了40%和70%。相反，在肾上腺、上级颈神经节、松果体和视网膜中未发现受体结合位点密度的显著变化。这些数据表明，即使在高剂量下长期给予尼古丁也不会增加所有烟碱受体亚型，并且含有α 3亚基的受体可能对这种尼古丁诱导的变化特别耐受。
Neuronal nicotinic acetylcholine receptors (nAChRs) were measured in CNS and peripheral tissues following continuous exposure to saline or nicotine hydrogen tartrate (3.3 or 10 mg/kg/day) for 14 days via osmotic pumps. Initially, binding of [(3) H](-)nicotine, [(3) H]cytisine and [(3) H]epibatidine to nAChRs was compared to determine the suitability of each for these kinds of studies. The predominant nAChR labeled by agonists in the cerebral cortex is an alpha4beta2 subtype, whereas the predominant nicotinic receptors in the adrenal gland, superior cervical ganglia and pineal gland contain an alpha3 subunit, and they do not bind either [(3) H](-)nicotine or [(3) H]cytisine with high affinity. In retina some nAChRs bind all three ligands with high affinity, and others appear to bind only [(3) H]epibatidine. Thus, only [(3) H]epibatidine had high enough affinity to be useful for measuring the nAChRs in all of the tissues. The receptors from nicotine-treated rats were then measured using [(125) I]epibatidine, which has binding characteristics very similar to [(3) H]epibatidine. Treatment with the two doses of nicotine hydrogen tartrate increased binding sites in the cerebral cortex by 40% and 70%, respectively. In contrast, no significant changes in the density of receptor binding sites were found in the adrenal gland, superior cervical ganglia, pineal gland or retina. These data indicate that chronic administration of nicotine even at high doses does not increase all nicotinic receptor subtypes, and that receptors containing alpha3 subunits may be particularly resistant to this nicotine-induced change.