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尼古丁对视网膜中cGMP/一氧化氮信号转导系统的激活作用。

Activation of the cGMP/nitric oxide signal transduction system by nicotine in the retina.

作者信息

Blute Todd A, Strang Christianne, Keyser Kent T, Eldred William D

机构信息

Department of Biology, Boston University, Boston, MA 02215, USA.

出版信息

Vis Neurosci. 2003 Mar-Apr;20(2):165-76. doi: 10.1017/s0952523803202078.

DOI:10.1017/s0952523803202078
PMID:12916738
Abstract

Acetylcholine is one of the primary excitatory neurotransmitters/neuromodulators in the retina, but little is known about the downstream signaling pathways it can activate. The present study immunocytochemically examines the potential sources of acetylcholine and the location of the nicotinic cholinergic receptors in the turtle retina. It also examines how activation of these receptors can influence the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signal-transduction pathways. Photoreceptors, amacrine cells, and potentially ganglion cells contain choline acetyltransferase-like immunoreactivity (LI). Nicotinic acetylcholine receptors are immunocytochemically localized on photoreceptors, horizontal, bipolar, and ganglion cells. Nitric oxide imaging indicates that stimulation with nicotine increases NO production primarily in photoreceptors, horizontal, Muller, bipolar, and ganglion cells. In turn, very select populations of amacrine cells respond to this NO with increased levels of cGMP-LI. Selective inhibitors reveal that nitric oxide synthase is involved in most, but not all, of these increases in cGMP-LI. These results show that acetylcholine can activate the NO/cGMP signal-transduction pathways in both the inner and outer retina. This indicates that both of the major excitatory retinal transmitters, glutamate and acetylcholine, can stimulate NO production that increases levels of cGMP-LI in overlapping populations of retinal cells.

摘要

乙酰胆碱是视网膜中主要的兴奋性神经递质/神经调质之一,但人们对其可激活的下游信号通路知之甚少。本研究采用免疫细胞化学方法检测了乙酰胆碱的潜在来源以及烟碱型胆碱能受体在龟视网膜中的定位。研究还探讨了这些受体的激活如何影响一氧化氮(NO)/环磷酸鸟苷(cGMP)信号转导通路。光感受器、无长突细胞以及可能的神经节细胞含有胆碱乙酰转移酶样免疫反应性(LI)。烟碱型乙酰胆碱受体通过免疫细胞化学方法定位在光感受器、水平细胞、双极细胞和神经节细胞上。一氧化氮成像显示,尼古丁刺激主要使光感受器、水平细胞、穆勒细胞、双极细胞和神经节细胞中的一氧化氮生成增加。反过来,非常特定的无长突细胞群体对这种一氧化氮的反应是cGMP-LI水平升高。选择性抑制剂表明,一氧化氮合酶参与了大部分(但不是全部)cGMP-LI的升高。这些结果表明,乙酰胆碱可激活视网膜内外的NO/cGMP信号转导通路。这表明视网膜的两种主要兴奋性神经递质,即谷氨酸和乙酰胆碱,均可刺激一氧化氮生成,从而使视网膜细胞重叠群体中的cGMP-LI水平升高。

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