Cellular and Molecular Neurobiology

, Volume 25, Issue 5, pp 819–832 | Cite as

Co-activation of P2Y2 Receptor and TRPV Channel by ATP: Implications for ATP Induced Pain

  • Srihasam Lakshmi
  • Preeti G. Joshi


  1. 1.

    Extracellular ATP is recognized as a peripheral modulator of pain. Activation of ionotropic P2X receptors in sensory neurons has been implicated in induction of pain, whereas metabotropic P2Y receptors in potentiation of pain induced by chemical or physical stimuli via capsaicin sensitive TRPV1 channel. Here we report that P2Y2 receptor activation by ATP can activate the TRPV1 channel in absence of any other stimuli.

  2. 2.

    ATP-induced Ca2 + signaling was studied in Neuro2a cells. ATP evoked release of intracellular Ca2 + from ER and Ca2 + influx through a fast inactivating channel. The Ca2 + response was induced by P2Y receptor agonists in the order of potency ATP ≥ UTP ≥ ATPγ S > ADP and was inhibited by suramin and PPADS. The P2X receptor agonist α β methyl ATP was ineffective.

  3. 3.

    The Ca2 + influx was blocked by ruthenium red, an inhibitor of TRPV1 channel. Capsaicin, the most potent activator of the TRPV1 channel, evoked a fast inactivating Ca2 + transient suggesting the presence of endogenous TRPV1 channels in Neuro2a cells. NMS and PDBu, repressors of IP3 formation, drastically inhibited both the components of Ca2 + response.

  4. 4.

    Our data show co-activation of the P2Y2 receptor and capsaicin sensitive TRPV1 channel by ATP. Such functional interaction between endogenous P2Y2 receptor and TRPV1 channels could explain the ATP-induced pain.



P2Y2 receptor TRPV channel capsaicin receptor extracellular ATP nociception Neuro2a cells intracellular Ca2 + Fura-2 



adenosine 5′-diphosphate


adenosine 5′-monophosphate


adenosine 5′-triphosphate


adenosine 5′-[γ -thio]triphosphate

αβ methyl ATP

α,β-methylene adenosine 5′-triphosphate

2 Me-S-ATP

2(methyl thio) adenosine 5′-triphosphate


capacitative calcium entry


cyclopiazonic acid


ethylene glycol-bis (2-aminoethylether)-N,N,N′,N′-tetraacetic acid


guanosine 5′-triphoshate


inositol 1,4,5-triphosphate


neomycin sulphate


phorbol 12,13-dibutyrate


pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid)




protein kinase C


phosholipase C


pertussis toxin


store-operated calcium entry


transient receptor potential channel, subfamily V


transient receptor potential channel, subfamily C


uridine 5′-diphoshate


uridine 5′-triphoshate


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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Srihasam Lakshmi
    • 1
  • Preeti G. Joshi
    • 1
  1. 1.Department of BiophysicsNational Institute of Mental Health and NeurosciencesBangaloreIndia

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