BioAcyl Corp
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Ambrosino, P., Soldovieri, M. V., & Russo, C. (2013). Activation and desensitization of trpv1 channels in sensory neurons by the pparα agonist palmitoylethanolamide. British Journal of Pharmacology, 168(6), 1430–1444. Added by: Dr. Enrique Feoli (17/12/2023, 18:01) Last edited by: Dr. Enrique Feoli (17/12/2023, 18:03) |
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| Resource type: Journal Article DOI: https://doi.org/10.1111/bph.12029 BibTeX citation key: Ambrosino2013 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Analgesia Creators: Ambrosino, Russo, Soldovieri Collection: British Journal of Pharmacology |
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| Abstract |
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Background and Purpose Palmitoylethanolamide (PEA) is an endogenous fatty acid amide displaying anti-inflammatory and analgesic actions. To investigate the molecular mechanism responsible for these effects, the ability of PEA and of pain-inducing stimuli such as capsaicin (CAP) or bradykinin (BK) to influence intracellular calcium concentrations ([Ca2+]i) in peripheral sensory neurons, has been assessed in the present study. The potential involvement of the transcription factor PPARα and of TRPV1 channels in PEA-induced effects was also studied. Experimental Approach [Ca2+]i was evaluated by single-cell microfluorimetry in differentiated F11 cells. Activation of TRPV1 channels was assessed by imaging and patch-clamp techniques in CHO cells transiently-transfected with rat TRPV1 cDNA. Key Results In F11 cells, PEA (1–30 μM) dose-dependently increased [Ca2+]i. The TRPV1 antagonists capsazepine (1 μM) and SB-366791 (1 μM), as well as the PPARα antagonist GW-6471 (10 μM), inhibited PEA-induced [Ca2+]i increase; blockers of cannabinoid receptors were ineffective. PEA activated TRPV1 channels heterologously expressed in CHO cells; this effect appeared to be mediated at least in part by PPARα. When compared with CAP, PEA showed similar potency and lower efficacy, and caused stronger TRPV1 currents desensitization. Sub-effective PEA concentrations, closer to those found in vivo, counteracted CAP- and BK-induced [Ca2+]i transients, as well as CAP-induced TRPV1 activation. Conclusions and Implications Activation of PPARα and TRPV1 channels, rather than of cannabinoid receptors, largely mediate PEA-induced [Ca2+]i transients in sensory neurons. Differential TRPV1 activation and desensitization by CAP and PEA might contribute to their distinct pharmacological profile, possibly translating into potentially relevant clinical differences.
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