Production of nitric oxide by glial cells: regulation and potential roles in the CNS.
Roles proposed for nitric oxide (NO) in CNS pathophysiology are increasingly diverse and range from intercellular signaling, through necrotic killing of cells and invading pathogens, to the involvement of NO in apoptosis and tissue remodeling. In vitro evidence and observations from experimental animal models of a variety of human neuropathologies, including stroke, indicate that glial cells can produce NO. Regulation of at least one of the NO synthase genes (NOS-2) in glia has been well described; however, apart from hints emerging out of co-culture studies and extrapolation based upon the reactivity of NO, we are a long way from identifying functions for glial-derived NO in the CNS. Although the assumption is that NO is very often cytotoxic, it is evident that NO production does not always equate with tissue damage, and that both the cellular source of NO and the timing of NO production are important factors in terms of its effects. With the development of strategies to transfer or manipulate expression of the NOS genes in specific cells in situ, the ability to deliver NO into the CNS via long-lived chemical donors, and the emergence of more selective NOS inhibitors, an appreciation of the significance of glial-derived NO will change.
Murphy
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Department of Pharmacology and the Neuroscience Program, University of Iowa College of Medicine, Iowa City, USA. sean.murphy@nottingham.ac.uk
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism; D002490:Central Nervous System / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D002493:Central Nervous System Diseases / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008024:Ligands; D008297:Male; D051379:Mice; D009457:Neuroglia / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D015533:Transcriptional Activation; D014777:Virus Diseases / Q000378:metabolism
D007527:Isoenzymes; D008024:Ligands; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase