Metabotropic P2Y1 receptors inhibit P2X3 receptor-channels in rat dorsal root ganglion neurons.
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.
Gerevich
Zoltan
Z
Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Haertelstrasse 16-18, D-04107 Leipzig, Germany. Zoltan.Gerevich@medizin.uni-leipzig.de
Müller
Christoph
C
Illes
Peter
P
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058477:Receptors, Purinergic P2X3; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides / Q000494:pharmacology
C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; C546410:P2rx3 protein, rat; C546384:P2ry1 protein, rat; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides; C034883:guanosine 5'-O-(2-thiotriphosphate); C002480:methylthio-ADP; C030812:adenosine 5'-O-(2-thiodiphosphate); D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; C117446:cangrelor; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; C002630:alpha,beta-methyleneadenosine 5'-triphosphate