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Adenosine regulating enzymes as indicators of excitotoxicity

James Woodson jwoodson at ucla.edu
Thu Jul 11 13:09:39 EST 1996

To those concerned:  I sent the following to Dr. Karim Brohi per the
posting on neuronal products of anaerobic metabolism.  Does anyone else
have some informed feedback for me on adenosine, its regulating enzymes, or
other indices of neural trauma (e.g, glutemate cascade, etc.)?
        Feel free to reply directly, so as not to clutter other
mailboxes... jwoodson at ucla.edu

Thanks,  James Woodson

Adenosine is often released under conditions of metabolic stress, as in
anoxia, hypoxia, ischemia, and can be be released by chemical or electrical
brain stimulation (Sciotti,  Park, Berne, & VanWylen, 1993). When neuronal
energy production (i.e, ATP production) fails to keep up with ATP breakdown
supplying energy to the cell, adenosine builds up, is extruded throught the
membrane, and works both pre- and post-synaptically to "shut down" the
cells, allowing homeostatic recovery to proceed.  Seeing as this is
occurring during potentially excitotoxic conditions (Headrick, Bendall,
Faden, & Vink, 1994, Martin, Lloyd, & Cowan, 1994), having been proposed as
a "retaliatory metabolite" by Newby (1984), and recognized as a
neuroprotective agent by many others (e.g., Stone, 1981; 1991), it is a
primary candidate for assessing neuronal injury post-trauma.  Keep in mind,
however, that some evidence of tonic adenosine activity exists for example
in the hippocampus (Alzheimer et al., 1991, 1993).  Therefore, using the
activity of breakdown enzymes such as adenosine deaminase and adenosine
kinase might be a better way to detect larger amounts being released in a
site-specific manner.  Here are some helpfull references.  Let me know what
you find.

1       Alzheimer, C., Sutor B. and ten Bruggencate G., Disinhibition of
hippocampal CA3 neurons induced by suppression of an adenosine A1
receptor-mediated inhibitory tonus: pre- and postsynaptic  components.,
Neuroscience, 57 (1993) 565-575.

2       Alzheimer, C. and ten Bruggencate G., Postsynaptic inhibition by
adenosine in hippocampal CA3 neurons:  Co(2+)-sensitive activation of an
inwardly rectifying K+ conductance., Pflugers Archives of European Journal
of Physiology, 419 (1991) 288-295.

3       Headrick, J. P., Bendall M. R., Faden A. I. and Vink R.,
Dissociation of adenosine levels from bioenergetic state in experimental
brain trauma:   Potential role in secondary injury., 14, 853 - 861.,
Journal of Cerebral Blood Flow and Metabolism, 14 (1994) 853-861.

4       Martin, L. R., Lloyd H. G. E. and Cowan A. I., The early events of
oxygen and glucose deprivation:  Setting the scene for neuronal death?,
Trends in Neuroscience,, 17 (1994) 251-256.

5       Newby, A. C., Adenosine and the concept of "retaliatory
metabolites.", Trends in Biochemical Science, 9 (1984) 42-44.

6       Sciotti, V. M., Park T. S., Berne R. M. and VanWylen D. G. L.,
Changes in extracellular adenosine during chemical or electrical brain
stimulation., Brain Research, 613 (1993) 16-20.

7       Stone, T. W., Physiological roles of adenosine and adenosine
5'triphosphate in the nervous system., Neuroscience, 6 (1981) 523 - 555.

8       Stone, T. W., Adenosine as a neuroactive compound in the central
nervous system. In J. W. Phillis (Ed.), Adenosine and Adenine Nucleotides
as Regulators of Cellular Function., CRC Press, Boca Raton, 1991, pp. 329

James Woodson (jwoodson at ucla.edu)
Dept. of Psychology - Behavioral Neuroscience
University of California at Los Angeles
405 Hilgard Ave.
Los Angeles, CA 90095

 People are about as happy as they make up their minds to be.
          -  Abraham Lincoln

*Research in Learned Helplessness, Adenosine,
 Sex Differences in the Brain (SDN-POA), and Sexual Motivation

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