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Development of an electrochemical adenosine sensor: Understanding the function of transient adenosine in the brain

    We are characterizing the electrochemistry of adenosine at carbon-fiber microelectrodes.  While dopamine has been extensively studied using carbon-fiber microelectrodes, the technique has not been widely applied to many of other neurochemicals.  Adenosine is a neuromodulator in the brain that has a variety of actions including regulation of cerebral blood flow, modulation of neurotransmission, and protection against neuronal injury during stroke.  No reliable method currently exists for electrochemical detection of adenosine in vivo.
    Our lab developed an electrochemical method for subsecond detection of adenosine release.  Using that, we have discovered transient adenosine release in vivo and in brain slices.  Our lab was the first to characterize 3 s duration adenosine transients that can modulate dopamine neurotransmission and blood flow.  We are currently looking at both the mechanism of adenosine formation and the function of adenosine.    Simultaneous detection of adenosine and oxygen is possible so we are studying the effects of adenosine on blood flow. 
This method is being used to characterize the mechanisms of adenosine formation in brain slices and to detect spontaneous transient adenosine release in anesthetized rats.  We are also interested in studying transient adenosine release during disorders such as stroke. 

              Theophylline

In vivo studies of the effects of adenosine.  Dopamine, pH, and oxygen changes were measured before (left) and after (right) administration of theophylline, an adenosine receptor antagonist.  Applied voltage is the y-axis, elapsed time the x-axis and measured current is in color.  The top traces, taken from the color plots, show concentration changes over time.  Adenosine receptor antagonism reduces the second peak of oxygen changes.

Adenosine

Pathways of adenosine formation.  Adenosine can be formed intracellulary and then transported out of the neuron or extracellulary after the breakdown of released ATP.

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