A ₁ receptors inhibit glutamate release in rat medullary dorsal horn neurons

We have investigated the adenosine-mediated presynaptic inhibition of primary afferent-evoked glutamate release in rat substantia gelatinosa neurons of the trigeminal subnucleus caudalis using a conventional whole-cell patch clamp technique. Adenosine reversibly and concentration dependently decreased the amplitude of glutamatergic excitatory postsynaptic currents and increased the paired-pulse ratio, indicating that adenosine acts presynaptically to reduce glutamate release from primary afferents. The adenosine-induced inhibition of excitatory postsynaptic currents was occluded by a selective A ₁ receptor antagonist, DPCPX, and was mimicked by a selective A ₁ receptor agonist CPA. The results suggest that presynaptic A ₁ receptors decrease action potential-dependent glutamate release from trigeminal primary afferents onto medullary dorsal horn neurons, and thus adenosine A ₁ receptors could be a potential target for the treatment of pain of orofacial tissues.