Physiologic role for“inducible”nitric oxide synthase:A new form of astrocytic-neuronal interface

长期以来,一氧化氮(NO)都被看作是影响兴奋性突触传递的非典型神经信使分子,其细胞来源尚不清楚。许多脑区中的神经元型一氧化氮合酶(nNOS)只在少量抑制性神经元中表达。众所周知,胶质细胞诱导型一氧化氮合酶(iNOS)不在正常大脑中表达,其在免疫刺激后可经转录介导上调。因此,iNOS调节正常神经功能的作用常被忽视。许多研究表明,有功能的iNOS存在于哺乳动物的正常脑区,包括星形胶质细胞。NO可通过iN-OS调节突触前膜的递质释放。据以上研究结果推测,正常脑组织中,星形胶质细胞表达基础水平的iNOS,被激活后,星形胶质细胞可释放NO并影响突触释放。

Nitric oxide（NO） has been long recognized as an atypical neuronal messenger affecting excitatory synaptic transmission,but its cellular source has remained unresolved as the neuronal isoform of NO synthase（nNOS） in many brain regions is expressed only by small subsets of inhibitory neurons.It is generally believed that the glial NO-producing isoform（iNOS） is not expressed in the normal brain,but rather it undergoes a transcription-mediated up-regulation following an immunological challenge.Therefore,the involvement of iNOS in modulating normal neuronal functions has been largely ignored.Here I review evidence to the contrary：I summarize data pointing to the existence of a functioning iNOS in normal undisturbed mammalian brains,and experimental results tracing this expression to astrocytes.Finally,I review recent findings asserting that iNOS-dependent NO modulates synaptic release from presynaptic terminals.Based on these data,I propose that astrocytes express basal levels of iNOS.Flanking synaptic elements,astrocytes are perfectly positioned to release NO and affect synaptic transmission.