Transient Adenosine Release Is Modulated by NMDA and GABAB Receptors

Abstract

<p class="first" id="P1">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 A ₁ and A _2a receptors, 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 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 GABA _B antagonist CGP 52432 (30 mg/kg i.p.) significantly decreased the number of adenosine release events while the GABA _B agonist baclofen (4 mg/kg i.p.) increased the frequency of adenosine release. The GABA _A antagonist bicuculline (5 mg/kg i.p.) had no significant effects on adenosine. NMDA and GABA _B likely act presynaptically, affecting the overall cell excitability for vesicular release. The ability to regulate adenosine with NMDA and GABA _B receptors will help control the modulatory effects of transient adenosine release. </p>