Cholinergic activity modulates the survival of retinal ganglion cells in culture:: the role of M1 muscarinic receptors
Cholinergic activity modulates the survival of retinal ganglion cells in culture:: the role of M1 muscarinic receptors
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DOI：
10.1016/s0736-5748(01)00043-0
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发表时间：
2001-10-01
影响因子：
1.8
通讯作者：
Araujo, EG
中科院分区：
文献类型：
--
作者：
Pereira, SPF;Medina, SV;Araujo, EG
自然细胞死亡的控制是由靶细胞、传入细胞和神经胶质细胞释放的神经营养因子介导的。在目前的工作中，我们表明，用 25 μM 氨甲酰胆碱“体外”处理视网膜细胞 48 小时，可使视网膜神经节细胞的存活率增加两倍。这种作用是剂量依赖性的，并由 M-1 受体介导，因为它可以被 1 muM 替仑西平（一种 M-1 受体拮抗剂）阻断，并被 200 muM 氧化震颤素（一种 M-1 受体激动剂）模拟。 10 μM BAPTA-AM（细胞内 Ca2+ 螯合剂）、30 μM 丹曲林（ryanodinic 受体抑制剂）、500 nM H-89（PKA 抑制剂）、1.25 μM 氯化白屈菜红碱（PKC 抑制剂）和 50 μM PD-98059（MEK）消除氨甲酰胆碱的作用。 抑制剂）。用 10 μM 金雀异黄素（酪氨酸激酶抑制剂）、25 μM LY-294002（一种 PI-3 激酶阻断剂）、30 nM brefeldin-A（多肽释放阻断剂）、50 nM K-252a（Trk 受体抑制剂）和 20 μM 氟脱氧尿苷（细胞增殖抑制剂）治疗完全抑制了 氨甲酰胆碱。总而言之，我们的结果表明，毒蕈碱活性通过涉及多肽释放和 Irk 受体激活的机制控制视网膜神经节细胞的存活。 (C) 2001 ISDN。爱思唯尔科学有限公司保留所有权利。
The control of natural cell death is mediated by neurotrophins released by target, afferent and glial cells. In the present work we show that treatment of retinal cells 'in vitro' for 48 h with 25 muM carbamylcholine induced a two-fold increase in retinal ganglion cells survival. This effect was dose-dependent and mediated by M-1 receptors since it could be blocked by 1 muM telenzepine (a M-1 receptor antagonist) and mimicked by 200 muM oxotremorine (a M-1 receptor agonist). The effect of carbamylcholine was abolished by 10 muM BAPTA-AM (an intracellular Ca2+ chelator), 30 muM dantrolene (an inhibitor of ryanodinic receptors), 500 nM H-89 (an inhibitor of PKA), 1.25 muM chelerythrine chloride (an inhibitor of PKC) and 50 muM PD-98059 (a MEK inhibitor). Treatment with 10 muM genistein (an inhibitor of tyrosine kinase), 25 muM LY-294002 (a PI-3 kinase blocker), 30 nM brefeldin-A (a blocker of polypeptides release), 50 nM K-252a (a Trk receptor inhibitor) and 20 muM fluorodeoxyuridine (an inhibitor of cell proliferation) totally inhibited the effect of carbamylcholine. Taken together our results indicate that muscarinic activity controls the survival of retinal ganglion cells through a mechanism involving the release of polypeptides and activation of Irk receptors. (C) 2001 ISDN. Elsevier Science Ltd. All rights reserved.