Phenotype-specific down-regulation of nicotinic acetylcholine receptors in the pelvic ganglia of castrated rats: Implications for neurogenic erectile dysfunction
Phenotype-specific down-regulation of nicotinic acetylcholine receptors in the pelvic ganglia of castrated rats: Implications for neurogenic erectile dysfunction
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去势大鼠盆腔神经节烟碱乙酰胆碱受体表型特异性下调：对神经源性勃起功能障碍的影响
DOI：
10.1016/j.neulet.2011.06.053
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发表时间：
2011-08-21
影响因子：
2.5
通讯作者：
Jeong, Seong-Woo
中科院分区：
文献类型：
--
作者：
Huang, Xue-Zhu;Park, Jong-Taek;Jeong, Seong-Woo
盆腔神经节 (PG) 在将交感神经和副交感神经信息从脊髓传递到阴茎脉管系统以及控制阴茎反射方面发挥着关键作用。动物研究表明，通过阉割剥夺雄激素会导致勃起功能障碍（ED）。然而，到目前为止，去势诱发 ED 的神经机制仍不清楚。因此，我们研究了雄激素剥夺是否会下调烟碱乙酰胆碱受体（nAchR），而烟碱乙酰胆碱受体介导 PG 中的快速兴奋性突触传递。为此，通过测量去势大鼠的海绵体内压来证明神经源性 ED。实时 PCR 分析显示，编码 nAchR α 3/α 5/β 4 亚基的转录本在 PG 神经元中显着下调。此外，通过替代睾酮可以逆转 nAchR 亚基的下调。膜片钳实验表明，nAchR 电流在支配阴茎脉管系统的副交感 PG 神经元中选择性减弱，其激活会引起阴茎勃起。综上所述，我们的数据表明，PG 神经元中 nAchR 的表型特异性下调可能导致去势大鼠的神经源性 ED。 (C) 2011 Elsevier Ireland Ltd. 保留所有权利。
Pelvic ganglia (PG) play critical roles in relaying sympathetic and parasympathetic information from the spinal cord to the penile vasculature and, controlling the penile reflex. Animal studies have shown that androgen deprivation by castration causes erectile dysfunction (ED). Until now, however, neural mechanisms underlying castration-induced ED remain unclear. Therefore, we examined whether androgen deprivation down-regulates nicotinic acetylcholine receptors (nAchRs), which mediate fast excitatory synaptic transmission in the PG. Toward this end, neurogenic ED was demonstrated by measuring the intracavernous pressure in castrated rats. Real-time PCR analysis revealed that the transcripts encoding nAchR alpha 3/alpha 5/beta 4 subunits were significantly down-regulated in the PG neurons. In addition, down-regulation of the nAchR subunits was reversed by replacement of testosterone. Patch-clamp experiments showed that the nAchR currents were selectively attenuated in the parasympathetic PG neurons innervating the penile vasculature, activation of which elicits penile erection. Taken together, our data suggest that phenotype-specific down-regulation of nAchRs in the PG neurons may contribute to the neurogenic ED in castrated rats. (C) 2011 Elsevier Ireland Ltd. All rights reserved.