Characterization of spontaneous, transient adenosine release in the caudate-putamen and prefrontal cortex.
Adenosine is a neuroprotective agent that inhibits neuronal activity and modulates neurotransmission. Previous research has shown adenosine gradually accumulates during pathologies such as stroke and regulates neurotransmission on the minute-to-hour time scale. Our lab developed a method using carbon-fiber microelectrodes to directly measure adenosine changes on a sub-second time scale with fast-scan cyclic voltammetry (FSCV). Recently, adenosine release lasting a couple of seconds has been found in murine spinal cord slices. In this study, we characterized spontaneous, transient adenosine release in vivo, in the caudate-putamen and prefrontal cortex of anesthetized rats. The average concentration of adenosine release was 0.17±0.01 µM in the caudate and 0.19±0.01 µM in the prefrontal cortex, although the range was large, from 0.04 to 3.2 µM. The average duration of spontaneous adenosine release was 2.9±0.1 seconds and 2.8±0.1 seconds in the caudate and prefrontal cortex, respectively. The concentration and number of transients detected do not change over a four hour period, suggesting spontaneous events are not caused by electrode implantation. The frequency of adenosine transients was higher in the prefrontal cortex than the caudate-putamen and was modulated by A1 receptors. The A1 antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine, 6 mg/kg i.p.) increased the frequency of spontaneous adenosine release, while the A1 agonist CPA (N(6)-cyclopentyladenosine, 1 mg/kg i.p.) decreased the frequency. These findings are a paradigm shift for understanding the time course of adenosine signaling, demonstrating that there is a rapid mode of adenosine signaling that could cause transient, local neuromodulation.
Department of Chemistry, University of Virginia, Charlottesville, Virginia, United States of America.
Michael D
MD
Nguyen
Department of Chemistry, University of Virginia, Charlottesville, Virginia, United States of America.
Scott T
ST
Lee
Department of Chemistry, University of Virginia, Charlottesville, Virginia, United States of America.
Ashley E
AE
Ross
Department of Chemistry, University of Virginia, Charlottesville, Virginia, United States of America.
Matthew
M
Ryals
Department of Chemistry, University of Virginia, Charlottesville, Virginia, United States of America.
Vishesh I
VI
Choudhry
Department of Chemistry, University of Virginia, Charlottesville, Virginia, United States of America.
B Jill
BJ
Venton
D000241:Adenosine / Q000378:metabolism*; D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D002244:Carbon; D000077482:Carbon Fiber; D008297:Male; D008839:Microelectrodes; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D043682:Receptor, Adenosine A1 / Q000378:metabolism
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000077482:Carbon Fiber; D043682:Receptor, Adenosine A1; D002244:Carbon; D000241:Adenosine