Metabotropic P2Y1 receptors inhibit P2X3 receptor-channels in rat dorsal root ganglion neurons

Eur J Pharmacol. 2005 Oct 3;521(1-3):34-8. doi: 10.1016/j.ejphar.2005.08.001. Epub 2005 Sep 19.

Abstract

Whole-cell patch-clamp recordings from cultured rat dorsal root ganglion neurons demonstrated that the P2Y1 receptor agonists adenosine 5'-O-2-thiodiphosphate (ADP-beta-S) and 2-methylthio adenosine 5'-diphosphate (2-MeSADP) inhibit the alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-meATP)-induced P2X3 receptor-currents. This effect could be antagonized by the wide-spectrum G protein blocker GDP-beta-S and the P2Y(1) receptor antagonist MRS 2179. The P2Y12,13 receptor antagonist AR-C6993MX and pertussis toxin, a blocker of Galphai/o, did not interact with the effect of ADP-beta-S. Hence, the results indicate that ADP-sensitive P2Y1 receptors of rat dorsal root ganglion neurons inhibit ionotropic P2X3 receptors via G protein-activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / analogs & derivatives
  • Adenosine Diphosphate / pharmacology
  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / pharmacology
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / physiology*
  • Guanosine 5'-O-(3-Thiotriphosphate) / analogs & derivatives
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Pertussis Toxin / pharmacology
  • Purinergic P2 Receptor Agonists
  • Purinergic P2 Receptor Antagonists
  • Rats
  • Rats, Wistar
  • Receptors, Purinergic P2 / physiology*
  • Receptors, Purinergic P2X3
  • Receptors, Purinergic P2Y1
  • Thionucleotides / pharmacology

Substances

  • N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate
  • P2rx3 protein, rat
  • P2ry1 protein, rat
  • Purinergic P2 Receptor Agonists
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X3
  • Receptors, Purinergic P2Y1
  • Thionucleotides
  • guanosine 5'-O-(2-thiotriphosphate)
  • methylthio-ADP
  • adenosine 5'-O-(2-thiodiphosphate)
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Adenosine Monophosphate
  • Adenosine Diphosphate
  • cangrelor
  • Adenosine Triphosphate
  • Pertussis Toxin
  • alpha,beta-methyleneadenosine 5'-triphosphate