P2Y2 receptors mediate ATP-induced resensitization of TRPV1 expressed by kidney projecting sensory neurons

Hui Wang, Donna H. Wang, James J. Galligan


The transient receptor potential vanilloid type 1 (TRPV1) channel is a ligand-gated cation channel expressed by sensory nerves. P2Y receptors are G protein-coupled receptors that are also expressed by TRPV1-positive sensory neurons. Therefore, we studied interactions between P2Y receptors and TRPV1 function on kidney projecting sensory neurons. Application of Fast Blue (FB) to nerves surrounding the renal artery retrogradely labeled neurons in dorsal root ganglia of rats. Whole cell recording was performed on FB-labeled neurons maintained in primary culture. Capsaicin was used to activate TRPV1. Four types of kidney projecting neurons were identified based on capsaicin responses: 1) desensitizing (35%), 2) nondesensitizing (29%), 3) silent (3%), and 4) insensitive (30%). Silent neurons responded to capsaicin only after ATP (100 μM) pretreatment. ATP reversed desensitization in desensitizing neurons. Insensitive neurons never responded to capsaicin. UTP, a P2Y purinoceptor 2 (P2Y2)/P2Y4 receptor agonist, reversed capsaicin-induced TRPV1 desensitization. 2-methyl-thio-ATP (2-Me-S-ATP), a P2Y1 receptor agonist, did not change desensitization. MRS 2179 and pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), drugs that block P2Y1 receptors, did not block ATP-induced resensitization of TRPV1. Suramin, a P2Y2 receptor antagonist, blocked resensitization caused by UTP. Immunocytochemical studies showed that FB-labeled neurons coexpressed P2Y2 receptors and TRPV1. We conclude that P2Y2 receptor activation can maintain TRPV1 function perhaps during sustained episodes of activity of kidney projecting sensory neurons.

  • dorsal root ganglia
  • capsaicin
  • desensitization
  • retrograde labeling
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