Pain. 2009 May;143(1-2):26-36. doi: 10.1016/j.pain.2009.01.006. Epub 2009 Feb 14.

Cross-inhibition between native and recombinant TRPV1 and P2X(3) receptors.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Stanchev, D., Blosa, M., Milius, D., Gerevich, Z., Rubini, P., Schmalzing, G., Eschrich, K., Schaefer, M., Wirkner, K., Illes, P.,
["Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Haertelstrasse 16-18, D-04107 Leipzig, Germany."]
Small- to medium-sized neurons in the dorsal root ganglion (DRG) convey nociceptive information to the spinal cord. The co-expression of TRPV1 receptors (sensitive to vanilloids, heat and acidic pH) with P2X(3) receptors (sensitive to extracellular ATP) has been found in many DRG neurons. We investigated whether the co-activation of these two receptor classes in small-diameter cells leads to a modulation of the resulting current responses shaping the intensity of pain sensation. The whole-cell patch clamp method was used to record agonist-induced currents in cultured rat DRG neurons and in HEK293 cells transfected with the respective wild-type recombinant receptors or their mutants. Co-immunoprecipitation studies were used to demonstrate the physical association of TRPV1 and P2X(3) receptors. At a negative holding potential, the P2X(3) receptor agonist alpha,beta-meATP induced less current in the presence of the TRPV1 agonist capsaicin than that in its absence. This inhibitory interaction was not changed at a positive holding potential, in a Ba(2+)-containing superfusion medium, or when the buffering of intrapipette Ca(2+) was altered. The C-terminal truncation at Glu362 of P2X(3) receptors abolished the TRPV1/P2X(3) cross-talk in the HEK293 expression system. Co-immunoprecipitation studies with polyclonal antibodies generated against TRPV1 and P2X(3) showed a visible signal in HEK293 cells transfected with both receptors. It is concluded that the two pain-relevant receptors TRPV1 and P2X(3) interact with each other in an inhibitory manner probably by a physical association established by a motif located at the C-terminal end of the P2X(3) receptor distal to Glu362.
PMID: 19223122External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Screening Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 P2RX3 Inference Prediction 19223122
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 P2RX3 Co-immunoprecipitation HEK293 Rat Full-length Human Full-length 19223122
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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