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Title: Regulation of extracellular arginine levels in the hippocampus in vivo
Author: Watts, Joanne
ISNI:       0000 0001 3564 5974
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2003
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Nitric oxide (NO) has emerged as an ubiquitous signaling molecule in the central nervous system (CNS). NO is synthesised from molecular oxygen and the amino acid L-arginine (L- ARG) by the enzyme NO synthase (NOS), and the availability of L-ARG has been implicated as the limiting factor for NOS activity. Previous studies have indicated that L- ARG is localised in astrocytes in vitro and that the in vitro activation of non-N-methyl-D- aspartate (NMDA) receptors, as well as the presence of peroxynitrite (ONOO ), led to the release of L-ARG. Microdialysis was therefore used in this study to investigate whether this held true in vivo. The results indicated that, while L-ARG was localised in glia in vivo and the infusion of α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) caused the release of L-ARG, this increase in extracellular L-ARG levels did not drive the NOS reaction. The increased L-ARG levels were halved by the coinfusion of CNQX but not totally inhibited. NMDA receptor activation is recognised as a major pathway of NOS activation and hence NO production and, while the results of this study concur, the results herein also suggest no need for increased L-ARG in the extracellular space as a prerequisite for NOS activation. Interesting results were also achieved using the NOS inhibitors Nw- nitro-L-ARG methyl ester (L-NAME) and 7-nitroindazole (7-NI). Both inhibitors increased the basal activity of NOS and production of NO, while each drug had contrasting effects on the NMDA-stimulated response. L-NAME blocked the increased NOS activity with no effect on NO production while 7-NI had no effect on NOS but blocked the production of NO. In conclusion, the regulation of the supply of L-ARG for NOS in vivo is far more complicated than in vitro studies suggest.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available