title: The ADP receptor P2Y1 is necessary for normal thermal sensitivity in cutaneous polymodal nociceptors.
abstract: BACKGROUND
  P2Y1 is a member of the P2Y family of G protein-coupled nucleotide receptors expressed in peripheral sensory neurons. Using ratiometric calcium imaging of isolated dorsal root ganglion neurons, we found that the majority of neurons responding to adenosine diphosphate, the preferred endogenous ligand, bound the lectin IB4 and expressed the ATP-gated ion channel P2X3. These neurons represent the majority of epidermal afferents in hairy skin, and are predominantly C-fiber polymodal nociceptors (CPMs), responding to mechanical stimulation, heat and in some cases cold.
  
  
  RESULTS
  To characterize the function of P2Y1 in cutaneous afferents, intracellular recordings from sensory neuron somata were made using an ex vivo preparation in which the hindlimb skin, saphenous nerve, DRG and spinal cord were dissected in continuum, and cutaneous receptive fields characterized using digitally-controlled mechanical and thermal stimuli in male wild type mice. In P2Y1-/- mice, CPMs showed a striking increase in mean heat threshold and a decrease in mean peak firing rate during a thermal ramp from 31-52°C. A similar change in mean cold threshold was also observed. Interestingly, mechanical testing of CPMs revealed no significant differences between P2Y1-/- and WT mice.
  
  
  CONCLUSIONS
  These results strongly suggest that P2Y1 is required for normal thermal signaling in cutaneous sensory afferents. Furthermore, they suggest that nucleotides released from peripheral tissues play a critical role in the transduction of thermal stimuli in some fiber types.
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Molliver
authors.forename: Kristofer K
authors.initials: KK
authors.lastname: Rau
authors.forename: Sabrina L
authors.initials: SL
authors.lastname: McIlwrath
authors.forename: Michael P
authors.initials: MP
authors.lastname: Jankowski
authors.forename: H Richard
authors.initials: HR
authors.lastname: Koerber
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004594:Electrophysiology; D006358:Hot Temperature; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009619:Nociceptors / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1 / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism; D012867:Skin / Q000294:innervation / Q000378:metabolism
chemical_list: D058472:Receptors, Purinergic P2Y1; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium