Activation and desensitization of TRPV1 channels in sensory neurons by the PPARα agonist palmitoylethanolamide

摘要: Background and Purpose Palmitoylethanolamide (PEA) is an endogenous fatty acid amide displaying anti-inflammatory analgesic actions. To investigate the molecular mechanism responsible for these effects, ability of PEA pain-inducing stimuli such as capsaicin (CAP) or bradykinin (BK) to influence intracellular calcium concentrations ([Ca2+]i) in peripheral sensory neurons, has been assessed present study. The potential involvement transcription factor PPARα TRPV1 channels PEA-induced effects was also studied. Experimental Approach [Ca2+]i evaluated by single-cell microfluorimetry differentiated F11 cells. Activation imaging patch-clamp techniques CHO cells transiently-transfected with rat cDNA. Key Results In cells, (1–30 μM) dose-dependently increased [Ca2+]i. antagonists capsazepine (1 μM) SB-366791 (1 μM), well antagonist GW-6471 (10 μM), inhibited [Ca2+]i increase; blockers cannabinoid receptors were ineffective. activated heterologously expressed cells; this effect appeared be mediated at least part PPARα. When compared CAP, showed similar potency lower efficacy, caused stronger currents desensitization. Sub-effective concentrations, closer those found vivo, counteracted CAP- BK-induced transients, CAP-induced activation. Conclusions Implications Activation channels, rather than receptors, largely mediate transients neurons. Differential activation desensitization CAP might contribute their distinct pharmacological profile, possibly translating into potentially relevant clinical differences.