Neurons, purine metabolism

There are important inhibitory systems built into the control of events following C-fibre stimulation. Thus, during peripheral noxious stimulation, spinal mechanism, driven by NMDA-receptor-mediated activity, can become active to damp down further neuronal responses, the purine, adenosine (see Chapter 13), appears to be involved in this type of control and has been reported to be effective in humans with neuropathic pain. It is thought that the depolarisations caused by activation of the NMDA receptor increase the metabolic demand on neurons and so ATP utilisation increases. ATP then is metabolised to adenosene and the purine then acts on its inhibitory Ai receptor in the... 

Purines such as ATP and adenosine play a central role in the energy metabolism of all life forms. This fact probably delayed recognition of other roles for purines as autocrine and paracrine substances and neurotransmitters. Today it is recognized that purines are released from neurons and other cells and that they produce widespread effects on multiple organ systems by binding to purinergic receptors located on the cell surface. The principal ligands for... 

ROS and RON can react with the DNA molecule and induce purine or p)u imidine base or sugar lesions, nitration and deaminations of purines, and DNA-DNA or DNA-protein cross-links (Dizdaroglu et al., 2002). These processes lead to mutations and impaired transcriptional and posttranscriptional processes and compromise protein synthesis (Colurso et al., 2003). In addition, DNA damage, oxidative phosphorylation, and altered cell metabolism may lead to apoptosis and promote neuronal death (Fishel et al., 2007 Becker and Bonni, 2004). ROS and RNS can also attack amino acids, leading to the formation of carbonyl derivatives (Stadtman and Levine, 2003). Oxidation of protein also leads to protein fragmentation and protein cross-linking. In addition, peroxynitrite and a hydroxyl radical can react with tyrosine and form other indexes of protein oxidation,... 

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