title: Transient Adenosine Release Is Modulated by NMDA and GABABReceptors.
abstract: Adenosine is a neuroprotective agent that modulates neurotransmission and is modulated by other neurotransmitters. Spontaneous, transient adenosine is a recently discovered mode of signaling where adenosine is released and cleared from the extracellular space quickly, in less than three seconds. Spontaneous adenosine release is regulated by adenosine A1and A2areceptors, but regulation by other neurotransmitter receptors has not been studied. Here, we examined the effect of glutamate and GABA receptors on the concentration and frequency of spontaneous, transient adenosine release by measuring adenosine with fast-scan cyclic voltammetry in the rat caudate-putamen. The glutamate NMDA antagonist, 3-(R-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 6.25 mg/kg i.p.), increased the frequency of adenosine transients and the concentration of individual transients, but NMDA (agonist, 50 mg/kg, i.p.) did not change the frequency. In contrast, antagonists of other glutamate receptors had no effect on the frequency or concentration of transient adenosine release, including the AMPA antagonist NBQX (15 mg/kg i.p.) and the mGlu2/3 glutamate receptor antagonist LY 341495 (5 mg/kg i.p.). The GABABantagonist CGP 52432 (30 mg/kg i.p.) significantly decreased the number of adenosine release events while the GABABagonist baclofen (4 mg/kg i.p.) increased the frequency of adenosine release. The GABAAantagonist bicuculline (5 mg/kg i.p.) had no significant effects on adenosine. NMDA and GABABlikely act presynaptically, affecting the overall cell excitability for vesicular release. The ability to regulate adenosine with NMDA and GABABreceptors will help control the modulatory effects of transient adenosine release.
authors.affiliation: Department of Chemistry and Neuroscience Graduate Program, University of Virginia , Charlottesville, Virginia 22904, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Nguyen
authors.affiliation: Department of Chemistry and Neuroscience Graduate Program, University of Virginia , Charlottesville, Virginia 22904, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Chemistry and Neuroscience Graduate Program, University of Virginia , Charlottesville, Virginia 22904, United States.
authors.forename: Mallikarjunarao
authors.initials: M
authors.lastname: Ganesana
authors.affiliation: Department of Chemistry and Neuroscience Graduate Program, University of Virginia , Charlottesville, Virginia 22904, United States.
authors.forename: B Jill
authors.identifier: 0000-0002-5096-9309
authors.initials: BJ
authors.lastname: Venton
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055664:Electrochemical Techniques; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D018683:Excitatory Amino Acid Agents; D018682:GABA Agents; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D000241:Adenosine
keywords: CGP 52432; CPP; GABAB; NMDA; Voltammetry; baclofen