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

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Summary

  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.

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Abbreviations

ADP:

adenosine 5′-diphosphate

AMP:

adenosine 5′-monophosphate

ATP:

adenosine 5′-triphosphate

ATPγS:

adenosine 5′-[γ -thio]triphosphate

αβ methyl ATP:

α,β-methylene adenosine 5′-triphosphate

2 Me-S-ATP:

2(methyl thio) adenosine 5′-triphosphate

CCE:

capacitative calcium entry

CPA:

cyclopiazonic acid

EGTA:

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

GTP:

guanosine 5′-triphoshate

IP3:

inositol 1,4,5-triphosphate

NMS:

neomycin sulphate

PDBu:

phorbol 12,13-dibutyrate

PPADS:

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

PIP2:

phosphoinositol-4,5-bisphosphate

PKC:

protein kinase C

PLC:

phosholipase C

PTx:

pertussis toxin

SOC:

store-operated calcium entry

TRPV:

transient receptor potential channel, subfamily V

TRPC:

transient receptor potential channel, subfamily C

UDP:

uridine 5′-diphoshate

UTP:

uridine 5′-triphoshate

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Authors and Affiliations

  1. Department of Biophysics, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, 560029, India

    Srihasam Lakshmi & Preeti G. Joshi

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  1. Srihasam Lakshmi
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  2. Preeti G. Joshi
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Lakshmi, S., Joshi, P.G. Co-activation of P2Y2 Receptor and TRPV Channel by ATP: Implications for ATP Induced Pain. Cell Mol Neurobiol 25, 819–832 (2005). https://doi.org/10.1007/s10571-005-4936-8

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  • DOI: https://doi.org/10.1007/s10571-005-4936-8

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