Elevated Levels of Ammonia Impair the NO/cGMP Through Alterations of Cellular Transporters~!

In other blogs, I have suggested that alterations in the NO/cGMP pathway by environmental factors may influence environmental disease including CFS and MCS. Several recent studies have suggested a relationship between the NO/cGMP pathway and the activation of the Nrf2. Because the Nrf2 has a neuroprotective role on astrocytes and neurons, the failure of this pathway could contribute to neurological damage commonly associated with aging as well as, other neurological disorders. In this most recent study, the author provides more evidence that in cases of hyperammonemia, the No/cGMP pathway activity is decreased and therefore, may provide some explanation for damage resulting from high ammonia levels.

"reduced delivery of Arg due to enhanced y(+)LAT2-mediated exchange of extracellular Gln for intracellular Arg may contribute to the decrease of NO/cGMP pathway activity evoked in the brain by HA."

Zielińska, M., Ruszkiewicz, J., Hilgier, W., Fręśko, I., and Albrecht, J. (2010). Hyperammonemia increases the expression and activity of the glutamine/arginine transporter y(+)LAT2 in rat cerebral cortex: implications for the nitric oxide/cGMP pathway. Neurochemistry international. http://www.citeulike.org/user/HEIRS/article/8341074
Sidoryk-Wegrzynowicz, M., Wegrzynowicz, M., Lee, E., Bowman, A., and Aschner, M. (2010). Role of Astrocytes in Brain Function and Disease. Toxicologic pathology.  http://www.citeulike.org/user/HEIRS/article/8341171

Astroglial Amino Acid Shuttle Involved in Nociceptive Pain Sensitization!

"This study has demonstrated that the central sensitization induced in functionally identified nociceptive neurons in trigeminal subnucleus caudalis (the medullary dorsal horn) by application of an inflammatory irritant to the rat's tooth pulp can be significantly attenuated by continuous intrathecal superfusion of methionine sulfoximine, an inhibitor of the astroglial enzyme glutamine synthetase that is involved in the glutamate–glutamine shuttle......Further, the lack of any observed significant effects of MSO alone, in contrast to our findings that it significantly attenuates MO-induced central sensitization, suggests that its action on astroglial GS is not evident in basal conditions but is apparent in hyperexcitable states, consistent with findings by ourselves and others that glia may not affect basal nociceptive processing but rather participate in exaggerated pain states. It is also noteworthy that an excess of glutamine in the CNS is involved in ammonia neurotoxicity possibly through its detrimental effects on mitochondrial function."

CiteULike: Astroglial Glutamate Glutamine Shuttle Is Involved in Central Sensitization of Nociceptive Neurons in Rat Medullary Dorsal Horn: "Chiang, C.-Y., Wang, J., Xie, Y.-F., Zhang, S., Hu, J. W., Dostrovsky, J. O., and Sessle, B. J. (2007). Astroglial glutamate glutamine shuttle is involved in central sensitization of nociceptive neurons in rat medullary dorsal horn. J. Neurosci., 27(34):9068-9076."


You might also like:

****

Mhalla, A., de Andrade, D. C. C., Baudic, S., Perrot, S., and Bouhassira, D. (2010). Alteration of cortical excitability in patients with fibromyalgia. Pain, 149(3):495-500.
http://www.citeulike.org/user/HEIRS/article/6962057
****
Chen, P.-C., Vargas, M. R., Pani, A. K., Smeyne, R. J., Johnson, D. A., Kan, Y. W., and Johnson, J. A. (2009). Nrf2-mediated neuroprotection in the mptp mouse model of parkinson's disease: Critical role for the astrocyte. Proceedings of the National Academy of Sciences, 106(8):2933-2938. http://www.citeulike.org/user/HEIRS/article/6551224?show_msg=already_posted