title: Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1).
abstract: 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 (EC50=37.9+/-1.9 microM) than capsaicin (EC50=0.29+/-0.05 microM), 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.
authors.affiliation: Neurology & GI-CEDD, GlaxoSmithKline, New Fronteirs Science Park, Third Avenue, Harlow, Essex CM19 5AW.
authors.forename: Fergal N
authors.initials: FN
authors.lastname: McNamara
authors.forename: Andrew
authors.initials: A
authors.lastname: Randall
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Gunthorpe
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D052117:Benzodioxoles; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018408:Patch-Clamp Techniques; D029222:Piper nigrum / Q000737:chemistry*; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides; D011955:Receptors, Drug / Q000819:agonists* / Q000037:antagonists & inhibitors*; D012430:Ruthenium Red / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011955:Receptors, Drug; D012430:Ruthenium Red; C071423:capsazepine; D002211:Capsaicin; C008922:piperine