Abstract
To date, eight subtypes of metabotropic P2Y receptors, P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13 and P2Y14 receptors, have been identified in mammals. Although numerous studies have demonstrated that ionotropic P2X receptors play a crucial role in facilitating pain transmission in the spinal cord, possible roles for P2Y receptors in nociceptive signaling have received limited attention. In this study, we examined whether the activation of P2Y receptors can modulate synaptic transmission in substantia gelatinosa (SG) neurons of adult rat spinal cord slices using whole-cell patch-clamp recordings. Bath application of UTP (100 μM), an agonist for P2Y2 and P2Y4 receptors, and UDP (100 μM), an agonist for P2Y6 receptors, affected neither excitatory (glutamatergic) nor inhibitory (glycinergic and/or GABAergic) synaptic transmission in all 11 SG neurons recorded. 2-Methylthio ADP (30 μM), an agonist for P2Y1, P2Y12 and P2Y13 receptors, also did not change excitatory transmission in all 11 SG neurons examined, but significantly increased the frequency and amplitude of spontaneous inhibitory (glycinergic and/or GABAergic) postsynaptic currents in 12 of 52 SG neurons recorded. These results indicate that the activation of 2-methylthio ADP-sensitive P2Y receptors enhances inhibitory but not excitatory synaptic transmission, probably through a direct action on spinal inhibitory interneurons. Thus, in contrast to P2X receptors, P2Y receptors can be involved in an inhibitory effect on pain transmission in the spinal dorsal horn. [J Physiol Sci. 2006;56 Suppl:S89]
