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

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 microM) pretreatment. ATP reversed desensitization in desensitizing neurons. Insensitive neurons never responded to capsaicin. UTP, a P2Y purinoceptor 2 (P2Y(2))/P2Y(4) receptor agonist, reversed capsaicin-induced TRPV1 desensitization. 2-methyl-thio-ATP (2-Me-S-ATP), a P2Y(1) receptor agonist, did not change desensitization. MRS 2179 and pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), drugs that block P2Y(1) receptors, did not block ATP-induced resensitization of TRPV1. Suramin, a P2Y(2) receptor antagonist, blocked resensitization caused by UTP. Immunocytochemical studies showed that FB-labeled neurons coexpressed P2Y(2) receptors and TRPV1. We conclude that P2Y(2) receptor activation can maintain TRPV1 function perhaps during sustained episodes of activity of kidney projecting sensory neurons

Keywords : Animals,Arteries,Capsaicin,cytology,drug effects,Drug Interactions,Ganglia,Spinal,Ion Channels,Kidney,Male,Mercaptoethanol,metabolism,Neurons,Neurons,Afferent,Patch-Clamp Techniques,pharmacology,physiology,Rats,Rats,Wistar,Receptors,Purinergic P2,Receptors,Purinergic P2Y2,Sensory Receptor Cells,Suramin,TRPV Cation Channels,Uridine Triphosphate,, Receptors,Mediate,Atpinduced,Resensitization, neck specialist london

Date of Publication : 2010 Jun

Authors : Wang H;Wang DH;Galligan JJ;

Organisation : Department of Physiology, Michigan State University, East Lansing, MI 48824, USA

Journal of Publication : Am J Physiol Regul Integr Comp Physiol

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/20335377

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