Opioidergic Regulation of P2X3 Receptor-Mediated Currents in DRG Neurons

Abstract

As is traditionally believed, the analgesic effects of opioids are due to their action on the CNS mechanisms. At present, however, proofs are been accumulated that activation of opioid receptors at the periphery can also result in a strong analgesic effect (especially in the case of inflammatory processes). In neurons of the dorsal root ganglia (DRG) of rats, we examined the effects of activation of opioid receptors on purinergic (P2X3) receptor-mediated ion currents and tried to identify possible intracellular signal pathways between the respective receptors. P2X3-mediated ion currents in DRG neurons were evoked by applications of αβ-Me-ATP. These currents were strongly (on average, by 74%) and reversibly inhibited after application of an endogenous opioid peptide, leu-enkephalin (L-Enk, 100 nM). A selective competitive antagonist of μ opioid receptors, CTOP, completely abolished the effect of L-Enk. We believe that a pathway mediated by phospholipase C (PLC) is involved in intracellular signaling between opioid and P2X3 receptors, and our experiments confirmed this hypothesis. A synthetic activator of PLC suppressed P2X3-mediated currents; an inhibitor of synthesis of phosphatidylinositol 4,5-bisphosphate (PIP2), wortmannin, accelerated and augmented the inhibitory effect of L-Enk on P2X3-mediated currents. Therefore, the inhibitory effect of L-Enk on the latter receptors is based on activation on PLC and hydrolysis of PIP2.