Nicotinic acetylcholine receptors in rat and human placenta
Nicotinic acetylcholine receptors in rat and human placenta
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DOI：
10.1016/j.placenta.2004.10.009
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发表时间：
2005-11-01
期刊：
影响因子：
3.8
通讯作者：
Kummer, W
中科院分区：
文献类型：
--
作者：
Lips, KS;Brüggmann, D;Kummer, W
怀孕期间吸烟会导致低出生体重、早产、新生儿发病率和死亡率。尼古丁是香烟烟雾的主要致病物质，可抑制人胎盘绒毛对氨基酸的摄取。它与烟碱型乙酰胆碱受体(NAChR)α亚基的乙酰胆碱结合部位结合。在哺乳动物中已经发现了八种不同的神经元nAChRα亚基。在这里，我们用RT-PCR和免疫荧光技术研究了它们在人和大鼠胎盘中的定位和分布。人和大鼠胎盘均表达所有α-亚基的mRNAs。免疫组织化学显示，α2-5、α7、α9和α10亚基在大鼠细胞滋养细胞、人和大鼠合体滋养细胞、血管平滑肌细胞、内皮细胞、Hofbauer细胞、人羊膜上皮和大鼠内脏卵黄囊上皮中以不同的组合分布。因此，所有类型的人和大鼠胎盘细胞都具有内源性配体ACh和尼古丁的结合位点的受体亚基。ACh被认为是一种重要的胎盘信号分子，通过对nAChR的刺激，在胎盘发育过程中控制营养物质的摄取、胎盘血管的血流和液体量以及血管形成。尼古丁对nAChR的慢性刺激可能会导致受体激活失衡或功能性脱敏，继而出现已知的吸烟病理效应。
Smoking during pregnancy causes low birth weight, premature delivery, neonatal morbidity, and mortality. Nicotine is a main pathogenic compound of cigarette smoke, and depresses active amino-acid uptake by human placental villi. It binds to the acetylcholine binding site of the alpha-subunits of nicotinic acetylcholine receptors (nAChR). Eight different neuronal nAChR alpha-subunits have been identified in mammals. Here, we investigated their localisation and distribution in the human and rat placenta by RT-PCR and immunofluorescence. The mRNAs of all a-subunits are expressed in the human and rat placenta. Immunohistochemically, subunits alpha 2-5, alpha 7, alpha 9 and alpha 10 are localised in different combinations in rat cytotrophoblast, human and rat syncytiotrophoblast, vascular smooth muscle cells, endothelial cells, Hofbauer cells, human amnion epithelium and rat visceral yolk sac epithelium. Thus, all human and rat placental cell types exhibit receptor subunits with binding sites for the endogenous ligand ACh and nicotine. ACh is suggested to be an important placental signalling molecule that, through stimulation of nAChR, controls the uptake of nutrients, blood flow and fluid volume in placental vessels, and the vascularisation during placental development. Chronic stimulation of nAChR by nicotine might result in unbalanced receptor activation or functional desensitisation followed by the known pathological effects of smoking.