Nitric oxide in brain: diffusion, targets and concentration dynamics in hippoca...

• Author(s): Ledo, Ana ; Frade, João ; Barbosa, Rui M. ; Laranjinha, João
• Date: 2004
• Persistent ID: http://hdl.handle.net/10316/5770
• Origin: Estudo Geral - Universidade de Coimbra
• Subject(s): Nitric oxide measurement; Nitric oxide dynamics; Nitric oxide signalling; Neurodegeneration; Hippocampus
• Document Type: Article
• Language: English

Description

Nitric oxide (NO[radical sign]) is a diffusible regulatory molecule involved in a wide range of physiological and pathological events. At the tissue level, a local and temporary increase in NO[radical sign] concentration is translated into a cellular signal. From our current knowledge of biological synthesis and decay, the kinetics and mechanisms that determine NO[radical sign] concentration dynamics in tissues are poorly understood. Generally, NO[radical sign] mediates its effects by stimulating (e.g., guanylate cyclase) or inhibiting (e.g., cytochrome oxidase) transition metal-containing proteins and by post-translational modification of proteins (e.g., formation of nitrosothiol adducts). The borderline between the physiological and pathological activities of NO[radical sign] is a matter of controversy, but tissue redox environment, supramolecular organization and compartmentalisation of NO[radical sign] targets are important features in determining NO[radical sign] actions. In brain, NO[radical sign] synthesis in the dependency of glutamate NMDA receptor is a paradigmatic example; the NMDA-subtype glutamate receptor triggers intracellular signalling pathways that govern neuronal plasticity, development, senescence and disease, suggesting a role for NO[radical sign] in these processes. Measurements of NO[radical sign] in the different subregions of hippocampus, in a glutamate NMDA receptor-dependent fashion, by means of electrochemical selective microsensors illustrate the concentration dynamics of NO[radical sign] in the sub-regions of this brain area. The analysis of NO[radical sign] concentration-time profiles in the hippocampus requires consideration of at least two interrelated issues, also addressed in this review. NO[radical sign] diffusion in a biological medium and regulation of NO[radical sign] activity. http://www.sciencedirect.com/science/article/B6T9P-4BY3ND9-2/1/f6c1c3e82caa2085d4b32f47150aba45