Nitric oxide in brain: diffusion, targets and concentration dynamics in hippocampal subregions.
Nitric oxide (NO(*)) 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(*) concentration is translated into a cellular signal. From our current knowledge of biological synthesis and decay, the kinetics and mechanisms that determine NO(*) concentration dynamics in tissues are poorly understood. Generally, NO(*) 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(*) is a matter of controversy, but tissue redox environment, supramolecular organization and compartmentalisation of NO(*) targets are important features in determining NO(*) actions. In brain, NO(*) 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(*) in these processes. Measurements of NO(*) 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(*) in the sub-regions of this brain area. The analysis of NO(*) concentration-time profiles in the hippocampus requires consideration of at least two interrelated issues, also addressed in this review. NO(*) diffusion in a biological medium and regulation of NO(*) activity.
Ledo
Ana
A
Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.
Frade
João
J
Barbosa
Rui M
RM
Laranjinha
João
J
D000818:Animals; D006624:Hippocampus / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology
D009569:Nitric Oxide