title: Interaction of A2A adenosine and D2 dopamine receptors modulates corticostriatal glutamatergic transmission.
abstract: Adenosine and dopamine (DA) strongly modulate the neuronal activity in the striatum by pre- and postsynaptic mechanisms. As several behavioral and molecular studies indicate a functional antagonism between A2A adenosine and D2 DA receptors, compounds that are able to block A2A receptors are of particular interest as antiparkinsonian agents. To study the interaction of A2A and D2 receptors in the striatum, we performed intracellular recordings with sharp microelectrodes and whole-cell patch clamp recordings from spiny neurons in rat corticostriatal slices. The amplitude of the evoked excitatory postsynaptic potentials (EPSPs), as well as the frequency and the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), were affected neither by the A2A receptor antagonists ST1535 and ZM241385, nor by the D2 receptor agonist quinpirole when applied in isolation. However, co-application of quinpirole and ST1535 or ZM241385 significantly reduced the EPSPs amplitude. This inhibitory effect was associated with an increased paired-pulse facilitation suggesting a presynaptic mechanism of action. Accordingly, whole-cell recordings showed that the concomitant activation of D2 receptors and the antagonism of A2A receptors decreased the frequency of sEPSCs without affecting their amplitude. These results suggest that A2A and D2 receptors converge in the control of corticostriatal glutamatergic transmission by exerting an opposite function.
authors: Clinica Neurologia, Università di Perugia, Ospedale S. Maria della Misericordia, 06156 Perugia, Italy.
authors: Alessandro
authors: A
authors: Tozzi
authors: Anne
authors: A
authors: Tscherter
authors: Vincenzo
authors: V
authors: Belcastro
authors: Michela
authors: M
authors: Tantucci
authors: Cinzia
authors: C
authors: Costa
authors: Barbara
authors: B
authors: Picconi
authors: Diego
authors: D
authors: Centonze
authors: Paolo
authors: P
authors: Calabresi
authors: Franco
authors: F
authors: Borsini
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010627:Phenethylamines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: C506291:2-n-butyl-9-methyl-8-(1,2,3)triazol-2-yl-9H-purin-6-ylamine; D018491:Dopamine Agonists; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019257:Quinpirole; D018698:Glutamic Acid; D000225:Adenine; D000241:Adenosine