Abstract
Intrathecal administration of adenosine analogues is well-known to result in an antinociception in the tail-flick test. Cellular mechanisms for this action of adenosine have not been fully examined yet, particularly in pharmacological properties, although adenosine receptors are classified into some subtypes including A1 and A2a receptors. We examined pharmacologically the action of adenosine on glutamatergic excitatory transmission to substantia gelatinosa (SG) neurons of an adult rat spinal cord slice with an attached dorsal root. Superfusing adenosine (100 µM) produced in SG neurons an outward current having a peak amplitude of 15 ± 5 pA (n=6). In 65% of the neurons examined (n=72), adenosine (100 µM) inhibited the frequency of miniature excitatory postsynaptic current (EPSC) in a reversible manner. When examined quantitatively in extent in some cells (n=25), the inhibition was 40 ± 3% (n=25); this was not accompanied by a change in miniature EPSC amplitude. The inhibitory action on miniature EPSC frequency was dose-dependent in a range of 10–500 µM with an EC50 value of 277 µM. The inhibitory action of adenosine was mimicked by a selective A1 adenosine receptor agonist, N6-cyclopentyladenosine (CPA, 1 µM; depression: 54 ± 9%, n=4); this action of adenosine (100 µM) was not observed in the presence of a specific A1 adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (1 µM). When examined for monosynaptic EPSCs evoked by electrical stimulation of the dorsal root, adenosine (100 µM) inhibited in amplitude Aδ-fiber EPSCs by 40 ± 5% in 9 of 17 neurons examined and C-fiber EPSCs by 34 ± 9% in 5 of 10 neurons examined. A similar inhibitory action was observed by CPA (1 µM). It is concluded that adenosine inhibits excitatory transmission to SG neurons from glutamatergic interneurons and primary-afferent neurons through the activation of presynaptic A1 adenosine receptors; this could serve to negatively modulate pain transmission to SG neurons from the periphery.
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