کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2561281 1560852 2014 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Functional and biochemical interaction between PPARα receptors and TRPV1 channels: Potential role in PPARα agonists-mediated analgesia
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Functional and biochemical interaction between PPARα receptors and TRPV1 channels: Potential role in PPARα agonists-mediated analgesia
چکیده انگلیسی

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-α peroxisome proliferator-activated receptors (PPARα) has been investigated. In TRPV1-expressing CHO cells, patch-clamp studies revealed that acute application of the PPARα agonists clofibrate (CLO; 0.1–100 μM), WY14643 (1–300 μM), or GW7647 (0.1–100 nM) activated TRPV1 currents in a concentration-dependent manner, with EC50s of 5.3 ± 0.8 μM, 13.0 ± 1.2 μM, and 12.7 ± 0.3 nM, respectively. The role of PPARα in these pharmacological responses was confirmed by the ability of the PPARα antagonist GW6471 (10 μM) to block CLO-, WY14643- and GW7647-induced TRPV1 activation, and by the observation that modulation of PPARα levels via siRNA-mediated suppression or PPARα over-expression affected TRPV1 channel activation by PPARα agonists accordingly. In cells cotransfected with PPARα and TRPV1, PPARα receptors were detected in TRPV1-immunoprecipitated fractions. When compared to capsaicin (CAP), TRPV1 currents activated by PPARα agonists showed a higher degree of acute desensitization and tachyphylaxis; moreover, GW7647, when pre-incubated at a concentration (1 nM) unable to activate TRPV1 currents per se, desensitized CAP-induced TRPV1 currents. Finally, a sub-effective concentration of each PPARα agonist inhibited TRPV1-dependent bradykinin-induced [Ca2+]i transients in sensory neurons. Collectively, these results provide evidence for a PPARα-mediated pathway triggering TRPV1 channel activation and desensitization, and highlight a novel mechanism which might contribute to the analgesic effects shown by PPARα agonists in vivo.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacological Research - Volume 87, September 2014, Pages 113–122
نویسندگان
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