Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1)

1 We have characterised the effects of piperine, a pungent alkaloid found in black pepper, on the human vanilloid receptor TRPV1 using whole‐cell patch‐clamp electrophysiology. 2 Piperine produced a clear agonist activity at the human TRPV1 receptor yielding rapidly activating whole‐cell currents that were antagonised by the competitive TRPV1 antagonist capsazepine and the non‐competitive TRPV1 blocker ruthenium red. 3 The current–voltage relationship of piperine‐activated currents showed pronounced outward rectification (25±4‐fold between −70 and +70 mV) and a reversal potential of 0.0±0.4 mV, which was indistinguishable from that of the prototypical TRPV1 agonist capsaicin. 4 Although piperine was a less potent agonist (EC 50 =37.9±1.9  μ M ) than capsaicin (EC 50 =0.29±0.05  μ M ), it demonstrated a much greater efficacy (approximately two‐fold) at TRPV1. 5 This difference in efficacy did not appear to be related to the proton‐mediated regulation of the receptor since a similar degree of potentiation was observed for responses evoked by piperine (230±20%, n =11) or capsaicin (284±32%, n =8) upon acidification to pH 6.5. 6 The effects of piperine upon receptor desensitisation were also unable to explain this effect since piperine resulted in more pronounced macroscopic desensitisation ( t 1/2 =9.9±0.7 s) than capsaicin ( t 1/2 >20 s) and also caused greater tachyphylaxis in response to repetitive agonist applications. 7 Overall, our data suggest that the effects of piperine at human TRPV1 are similar to those of capsaicin except for its propensity to induce greater receptor desensitisation and, rather remarkably, exhibit a greater efficacy than capsaicin itself. These results may provide insight into the TRPV1‐mediated effects of piperine on gastrointestinal function.British Journal of Pharmacology (2005) 144 , 781–790. doi: 10.1038/sj.bjp.0706040