Pharmacol Res. 2014 Sep;87:113-22. doi: 10.1016/j.phrs.2014.06.015. Epub 2014 Jul 8.

Functional and biochemical interaction between PPARalpha receptors and TRPV1 channels: Potential role in PPARalpha agonists-mediated analgesia.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Ambrosino, P., Soldovieri, M. V., De Maria, M., Russo, C., Taglialatela, M.,
["Dept. of Medicine and Health Sciences, University of Molise, Campobasso, Italy. Electronic address: paolo.ambrosino@unimol.it.", "Dept. of Medicine and Health Sciences, University of Molise, Campobasso, Italy. Electronic address: mariavirginia.soldovieri@unimol.it.", "Dept. of Medicine and Health Sciences, University of Molise, Campobasso, Italy. Electronic address: michela.demaria@studenti.unimol.it.", "Dept. of Medicine and Health Sciences, University of Molise, Campobasso, Italy. Electronic address: claudio.russo@unimol.it.", "Dept. of Medicine and Health Sciences, University of Molise, Campobasso, Italy; Dept. of Neuroscience, Section of Pharmacology, University of Naples Federico II, Naples, Italy. Electronic address: m.taglialatela@unimol.it."]
Transient receptor potential vanilloid type-1 (TRPV1) channels expressed in primary afferent neurons play a critical role in nociception triggered by endogenous and exogenous compounds. In the present study, the functional and biochemical interaction between TRPV1 channels and type-alpha peroxisome proliferator-activated receptors (PPARalpha) has been investigated. In TRPV1-expressing CHO cells, patch-clamp studies revealed that acute application of the PPARalpha agonists clofibrate (CLO; 0.1-100 muM), WY14643 (1-300 muM), or GW7647 (0.1-100 nM) activated TRPV1 currents in a concentration-dependent manner, with EC50s of 5.3 +/- 0.8 muM, 13.0 +/- 1.2 muM, and 12.7 +/- 0.3 nM, respectively. The role of PPARalpha in these pharmacological responses was confirmed by the ability of the PPARalpha antagonist GW6471 (10 muM) to block CLO-, WY14643- and GW7647-induced TRPV1 activation, and by the observation that modulation of PPARalpha levels via siRNA-mediated suppression or PPARalpha over-expression affected TRPV1 channel activation by PPARalpha agonists accordingly. In cells cotransfected with PPARalpha and TRPV1, PPARalpha receptors were detected in TRPV1-immunoprecipitated fractions. When compared to capsaicin (CAP), TRPV1 currents activated by PPARalpha agonists showed a higher degree of acute desensitization and tachyphylaxis; moreover, GW7647, when pre-incubated at a concentration (1nM) unable to activate TRPV1 currents per se, desensitized CAP-induced TRPV1 currents. Finally, a sub-effective concentration of each PPARalpha agonist inhibited TRPV1-dependent bradykinin-induced [Ca(2+)]i transients in sensory neurons. Collectively, these results provide evidence for a PPARalpha-mediated pathway triggering TRPV1 channel activation and desensitization, and highlight a novel mechanism which might contribute to the analgesic effects shown by PPARalpha agonists in vivo.
PMID: 25014183External 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 PPARơ Inference Prediction 25014183
(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 PPARơ Co-immunoprecipitation CHO Rat Full-length Rat Full-length 25014183
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Functional consequence Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
TRP channel Interactor Method Post-translational modification Subcellular trafficking Activity Reference
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PPARơ Calcium measurement Activation 25014183
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PPARơ Patch clamp Activation 25014183
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

To prevent spam comments, we use reCAPTCHA. Please type correct words into the following box.