Qian Y, Chao D S, Santillano D R, Cornwell T L, Nairn A C, Greengard P, Lincoln T M, Bredt D S
Department of Physiology, University of California San Francisco 94143, USA.
J Neurosci. 1996 May 15;16(10):3130-8. doi: 10.1523/JNEUROSCI.16-10-03130.1996.
Nitric oxide and cGMP influence plasticity of nociceptive processing in spinal cord. However, effectors for cGMP have not been identified in sensory pathways. We now demonstrate that cGMP-dependent protein kinase I (cGKl) occurs in the DRGs at levels comparable to that in cerebellum, the richest source of cGKl in the body. Immunohistochemical studies reveal that cGKl is concentrated in a subpopulation of small- and medium-diameter DRG neurons that partially overlap with substance P and calcitonin gene-related polypeptide containing cells. During development, cGKl expression throughout the embryo is essentially restricted to sensory neurons and to the spinal floor and roof plates. Neuronal nitric oxide synthase (nNOS) is coexpressed with cGKl in sensory neurons during embryonic development and after peripheral nerve axotomy. The primary target for cGKl in cerebellum, G-substrate, is not present in developing, mature, or regenerating sensory neurons, indicating that other proteins serve as effectors for cGKl in sensory processing. These data establish sensory neurons as a primary locus for cGMP actions during development and suggest a role for cGKl in plasticity of nociception.
一氧化氮和环磷酸鸟苷（cGMP）影响脊髓中伤害性处理的可塑性。然而，在感觉通路中尚未确定cGMP的效应器。我们现在证明，环磷酸鸟苷依赖性蛋白激酶I（cGKl）在背根神经节（DRG）中的水平与小脑相当，小脑是体内cGKl最丰富的来源。免疫组织化学研究表明，cGKl集中在中小直径DRG神经元的一个亚群中，这些神经元与含有P物质和降钙素基因相关肽的细胞部分重叠。在发育过程中，整个胚胎中的cGKl表达基本上仅限于感觉神经元以及脊髓底板和顶板。在胚胎发育期间和周围神经轴突切断后，神经元型一氧化氮合酶（nNOS）与cGKl在感觉神经元中共表达。小脑cGKl的主要靶点G底物在发育中的、成熟的或再生的感觉神经元中不存在，这表明其他蛋白质在感觉处理中作为cGKl的效应器。这些数据确定感觉神经元是发育过程中cGMP作用的主要位点，并提示cGKl在伤害感受可塑性中的作用。
