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乌龟视网膜中可溶性鸟苷酸环化酶的功能定位:一氧化氮供体对环磷酸鸟苷的调节

Functional localization of soluble guanylate cyclase in turtle retina: modulation of cGMP by nitric oxide donors.

作者信息

Blute T A, Velasco P, Eldred W D

机构信息

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

出版信息

Vis Neurosci. 1998 May-Jun;15(3):485-98. doi: 10.1017/s0952523898153075.

DOI:10.1017/s0952523898153075
PMID:9685201
Abstract

The second messenger cyclic guanosine monophosphate (cGMP) plays a role in many aspects of retinal processing. cGMP-gated channels function in photoreceptors, Müller, bipolar, and ganglion cells; and cGMP can modulate gap-junction conductivity. In the inner retina, both particulate and soluble guanylate cyclases can elevate levels of cGMP. The soluble isoform of guanylate cyclase is activated by nitric oxide (NO). In turtle retina, nitric oxide synthase, the enzyme that synthesizes NO, has been previously localized in discrete amacrine cells, somata in the ganglion cell layer, and in many processes in the inner plexiform layer. However, there have been no studies localizing soluble guanylate cyclase in the turtle retina. To functionally localize soluble guanylate cyclase, we stimulated retinas with the NO donors (+/-)-S-nitroso-N-acetylpenicillamine or spermine (nitric oxide) adduct, and then used immunocytochemistry to localize increases in cGMP-like immunoreactivity (cGMP-LI). The cells containing soluble guanylate cyclase should show cell autonomous increases in cGMP-LI in response to stimulation with NO. NO-stimulated increases in cGMP-LI occurred in many distinct amacrine cell types, select bipolar cells, some somata in the ganglion cell layer, and in discrete bands of processes in the inner plexiform layer. The pattern of cGMP-LI demonstrated qualitative dose response differences to the NO donors. This is the first localization of soluble guanylate cyclase in specific retinal neurons in the turtle; and the first functional activation of soluble guanylate cyclase in the amacrine cells of any species. The broad neuronal distribution of NO-stimulated cGMP-LI suggests that the NO/soluble guanylate cyclase/cGMP cascade is involved at several levels of visual processing in the inner retina.

摘要

第二信使环磷酸鸟苷(cGMP)在视网膜处理的许多方面发挥作用。cGMP门控通道在光感受器、穆勒细胞、双极细胞和神经节细胞中发挥功能;并且cGMP可以调节缝隙连接的传导性。在视网膜内层,颗粒型和可溶性鸟苷酸环化酶均可提高cGMP水平。可溶性鸟苷酸环化酶同工型可被一氧化氮(NO)激活。在龟视网膜中,合成NO的酶——一氧化氮合酶先前已被定位在离散的无长突细胞、神经节细胞层的胞体以及内网层的许多突起中。然而,此前尚无关于龟视网膜中可溶性鸟苷酸环化酶定位的研究。为了从功能上定位可溶性鸟苷酸环化酶,我们用NO供体(±)-S-亚硝基-N-乙酰青霉胺或精胺(一氧化氮)加合物刺激视网膜,然后使用免疫细胞化学方法来定位cGMP样免疫反应性(cGMP-LI)的增加。含有可溶性鸟苷酸环化酶的细胞在受到NO刺激时应表现出细胞自主性的cGMP-LI增加。NO刺激引起的cGMP-LI增加发生在许多不同类型的无长突细胞、特定双极细胞、神经节细胞层中的一些胞体以及内网层离散的突起带中。cGMP-LI模式显示出对NO供体的定性剂量反应差异。这是龟视网膜中可溶性鸟苷酸环化酶在特定视网膜神经元中的首次定位;也是任何物种无长突细胞中可溶性鸟苷酸环化酶的首次功能激活。NO刺激引起的cGMP-LI在神经元中的广泛分布表明,NO/可溶性鸟苷酸环化酶/cGMP级联参与了视网膜内层视觉处理的多个层面。

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