title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Fan
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Li-hua
authors.initials: LH
authors.lastname: Yu
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Ni
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Burnstock
authors.forename: Bei
authors.initials: B
authors.lastname: Ma
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D006727:Hormone Antagonists; D009419:Nerve Tissue Proteins; C546410:P2rx3 protein, rat; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D011980:Receptors, Progesterone; D058477:Receptors, Purinergic P2X3; D005576:Colforsin; D011374:Progesterone; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases