Group II metabotropic glutamate receptor activation suppresses ATP currents in rat dorsal root ganglion neurons

P2X3 receptors and group II metabotropic glutamate receptors (mGluRs) have been found to be expressed in primary sensory neurons. P2X3 receptors participate in a variety of pain processes, while the activation of mGluRs has an analgesic effect. However, it's still unclear whether there is a link between them in pain. Herein, we reported that the group II mGluR activation inhibited the electrophysiological activity of P2X3 receptors in rat dorsal root ganglia (DRG) neurons. Group II mGluR agonist LY354740 concentration-dependently decreased P2X3 receptor-mediated and alpha,beta-methylene-ATP (alpha,beta-meATP)-evoked inward currents in DRG neurons. LY354740 significantly suppressed the maximum response of P2X3 receptor to alpha,beta-meATP, but did not change their affinity. Inhibition of ATP currents by LY354740 was blocked by the group II mGluR antagonist LY341495, also prevented by the intracellular dialysis of either the Gi/o protein inhibitor pertussis toxin, the cAMP analog 8-Br-cAMP, or the protein kinase A (PKA) inhibitor H-89. Moreover, LY354740 decreased alpha,beta-meATP-induced membrane potential depolarization and action potential bursts in DRG neurons. Finally, intraplantar injection of LY354740 also relieved alpha,beta-meATP-induced spontaneous nociceptive behaviors and mechanical allodynia in rats by activating peripheral group II mGluRs. These results indicated that peripheral group II mGluR activation inhibited the functional activity of P2X3 receptors via a Gi/o protein and cAMP/PKA signaling pathway in rat DRG neurons, which revealed a novel mechanism underlying analgesic effects of peripheral group II mGluRs.

Automated summary

P2X3 receptors and group II mGluRs are expressed in primary sensory neurons. Activation of group II mGluRs inhibits the electrophysiological activity of P2X3 receptors. LY354740, a group II mGluR agonist, decreases the inward currents mediated by P2X3 receptors in rat DRG neurons.