Abstract
The present study examined the actions of adenosine on monosynaptic Aδ and C primary-afferent excitatory postsynaptic currents (EPSCs) recorded from substantia gelatinosa (SG) neurons of an adult rat spinal cord slice. In 67% of the neurons examined, adenosine reversibly decreased the amplitude of the Aδ-fiber EPSC, while in 13% of the neurons the amplitude was reduced or unaffected, which was followed by its increase persisting for several minutes after adenosine washout. The remaining neurons did not exhibit a change in the amplitude. The reduction in Aδ-fiber EPSC amplitude by adenosine was dose-dependent with an effective concentration for half-inhibition (EC 50) value of 217 μM. When examined by using a paired-pulse stimulus, a ratio of the second to first Aδ-fiber EPSC amplitude under the reduction was larger than that of EPSC amplitude in the control, suggesting a presynaptic action of adenosine. In 69% of the neurons tested, the C-fiber EPSC was reversibly decreased in amplitude by adenosine (100 μM) by an extent comparable to that of Aδ-fiber EPSC; the remaining neurons were without adenosine actions. Similar inhibitory actions of adenosine were also seen in neurons where both Aδ-fiber and C-fiber EPSCs were elicited. Similar reduction in the Aδ-fiber or C-fiber EPSC amplitude was induced by an A 1 adenosine-receptor agonist, N 6-cyclopentyladenosine (1 μM), and the adenosine-induced reduction was not observed in the presence of an A 1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (1 μM). An A 2a agonist, CGS 21680 (1 μM), did not significantly affect the Aδ-fiber EPSC amplitude. It is concluded that adenosine presynaptically inhibits monosynaptic Aδ-fiber and C-fiber transmission by a similar extent through the activation of the A 1 receptor in many but not all SG neurons; this could contribute to at least a part of antinociception by intrathecally administered adenosine analogues and probably by endogenous adenosine.
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