Progesterone Rapidly Attenuates ATP-Evoked Transient Currents in Cultured Rat Dorsal Root Ganglion Neurons

Abstract

Background: Progesterone has been shown to play a role in pain perception. However, the effects of progesterone on P2X3 receptors, the nociception-related receptors in primary sensory neurons, remain unclear. Methods: We investigated the effects of progesterone on P2X3-receptor-mediated responses of rat dorsal root ganglion neurons by using whole-cell patch clamp techniques. Results: Progesterone (10 pmol/l to 1 µmol/l) inhibited ATP (100 µmol/l)-induced transient currents and the transient component of biphasic currents in a dose-dependent manner, but had no effect on the sustained currents. The effect of progesterone could be blocked by its receptor inhibitor, RU38486. Actidione, an inhibitor of protein synthesis, did not change the rapid effect. Investigations of the signaling pathways of progesterone showed that a nonselective antagonist of protein kinase, H-9, totally blocked the depressive effect of progesterone on ATP currents in a dose-dependent manner. Blocking protein kinase A with H-89 or KT5720 also affected progesterone-induced depression. The protein kinase A activator, forskolin, mimicked the effect of progesterone on ATP currents. Conclusion: These results suggest that progesterone may modulate pain signal transmission on dorsal root ganglia via regulating P2X3 receptor function. The cAMP-PKA signaling pathway is involved in the downregulating effect of progesterone on P2X3 receptors.