Burette A, Petrusz P, Schmidt H H, Weinberg R J
Department of Cell Biology and Anatomy, University of North Carolina, CB 7090, Chapel Hill, NC 27599, USA.
J Comp Neurol. 2001 Feb 26;431(1):1-10. doi: 10.1002/1096-9861(20010226)431:1<1::aid-cne1051>3.0.co;2-e.
The diffusible messenger nitric oxide (NO) is implicated in auditory processing. It acts in the brain largely through activation of soluble guanylyl cyclase (sGC), a heterodimer comprised of alpha and beta subunits. The authors used immunohistochemistry to study the NO/guanosine 3',5'-cyclic monophosphate (cGMP) pathway in the cochlear nucleus of Sprague-Dawley rats. Central fibers of the cochlear nerve were stained for neuronal nitric oxide synthase (NOS-I) but not for sGCbeta. Within the ventral cochlear nucleus, a large fraction of principal cells were immunopositive for both NOS-I and sGCbeta; these cells could be seen at times receiving contacts from NOS-I-positive fibers. sGC staining of somatic cytoplasm extended into the distal dendritic tree. At variance with this pattern, NOS-I was concentrated mainly in somata. Double-labeling experiments showed that most of the principal neurons expressed both antigens. By contrast, in the granule cell domain, small cells that were immunopositive for NOS-I rarely corresponded to those that were immunopositive for sGC. To assess whether NOS-I and sGC immunoreactivities colocalize with their respective catalytic activities, the authors performed multiple labeling with L-citrulline (a by-product of the formation of NO from L-arginine) and cGMP, respectively. L-citrulline was restricted to NOS-I-positive elements, and the large majority of NOS-expressing neurons were positive for citrulline. Multiple labeling revealed that almost all sGC-positive neurons also accumulated cGMP both in the ventral cochlear nucleus and in the granule cell domain. These data suggest that NO is a signaling molecule in the cochlear nucleus, perhaps functioning in both a paracrine manner and an autocrine manner.
可扩散信使一氧化氮（NO）参与听觉处理过程。它在大脑中主要通过激活可溶性鸟苷酸环化酶（sGC）发挥作用，sGC是一种由α和β亚基组成的异二聚体。作者利用免疫组织化学方法研究了Sprague-Dawley大鼠耳蜗核中的NO/鸟苷3',5'-环磷酸（cGMP）信号通路。耳蜗神经的中枢纤维对神经元型一氧化氮合酶（NOS-I）呈阳性染色，但对sGCβ呈阴性染色。在腹侧耳蜗核内，大部分主细胞对NOS-I和sGCβ均呈免疫阳性；有时可见这些细胞接受NOS-I阳性纤维的接触。体细胞胞质的sGC染色延伸至远端树突。与这种模式不同的是，NOS-I主要集中在胞体。双重标记实验表明，大多数主神经元表达两种抗原。相比之下，在颗粒细胞区域，对NOS-I呈免疫阳性的小细胞很少与对sGC呈免疫阳性的细胞相对应。为了评估NOS-I和sGC免疫反应性是否与其各自的催化活性共定位，作者分别用L-瓜氨酸（L-精氨酸形成NO的副产物）和cGMP进行了多重标记。L-瓜氨酸仅限于NOS-I阳性元件，并且大多数表达NOS的神经元对瓜氨酸呈阳性。多重标记显示，几乎所有sGC阳性神经元在腹侧耳蜗核和颗粒细胞区域均积累cGMP。这些数据表明，NO是耳蜗核中的一种信号分子，可能以旁分泌和自分泌方式发挥作用。
