The role of adenosine A2a receptors in regulating GABAergic synaptic transmission in striatal medium spiny neurons.
We demonstrated an adenosine A2a receptor-mediated disinhibition of medium spiny projection neurons using intracellular recording and the whole-cell patch-clamp recording applied to these cells, visually identified in thin rat striatal slices. The A2a receptor agonist 2-[p-(2-carboxyethyl) phenylethylamino]-5'-N- ethylcarboxamido adenosine (CGS-21680; 0.3-10 microM) suppressed GABAergic synaptic transmission onto these cells in a manner inhibited by the A2a receptor-selective antagonist (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine (0.1-1.0 microM). The A1 receptor antagonists had no effect on the CGS-21680-induced suppression. Analysis of spontaneous miniature inhibitory synaptic currents indicated that suppression of intrastriatal GABAergic synaptic transmission was attributable to presynaptic, but not postsynaptic, A2a receptors. Therefore, the A2a receptor may regulate striatal output activity by relieving GABA-mediated inhibition of the medium spiny projection neurons, which explains the ability of purinergic agents to affect motor control.
Mori
A
A
Pharmaceutical Research Laboratory Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Shindou
T
T
Ichimura
M
M
Nonaka
H
H
Kase
H
H
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D010627:Phenethylamines; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D005680:gamma-Aminobutyric Acid; D000242:Cyclic AMP; D000241:Adenosine