Capsaicin-induced currents with distinct desensitization and Ca2+ dependence in rat trigeminal ganglion cells

Liu, L.; Simon, Sidney A.

doi:10.1152/jn.1996.75.4.1503

Cited by 167 publications

(124 citation statements)

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“…For GLNVA, the phenolic hydroxy group of the synthetic capsaicin analog nonanoyl-vanillamide is replaced by a glycerol moiety. Simon, 1996c). Moreover, we found that capsaicin can activate one ( Fig.…”

Section: Currents Activated By Capsaicin Olvanil and Glnvamentioning

confidence: 69%

“…The chamber containing the neurons had a volume of 500 l and was perfused continuously by KH flowing into the chamber at a rate of 6 ml/min (Liu and Simon, 1996c). In addition, capsaicin, olvanil, GLNVA, and capsazepine (Tocris Cookson, St. Louis, MO.)…”

Section: Methodsmentioning

confidence: 99%

“…To test whether 10 m capsazepine would inhibit the currents activated by olvanil or GLNVA, as it does those of capsaicin (Liu and Simon, 1996c), these two agonists (in KH buffer) were initially applied to the neurons for 32 sec. After washing for 3 min, 10 M capsazepine was applied to the cell for 3 min, and then a solution of capsazepine and olvanil or capsazepine and GLNVA was applied for 30 sec.…”

Section: Methodsmentioning

confidence: 99%

“…These inward currents can vary widely in their activation kinetics as characterized by the time to peak ( p). Although most had peak times between 1 and 9 sec (4.2 Ϯ 3.1; mean Ϯ SD) (Liu and Simon, 1996c) others had peak times of ϳ40 sec (41.4 Ϯ 16.4 sec; mean Ϯ SD) (Liu and Simon, 1996b) (Fig. 2 D).…”

Section: Currents Activated By Capsaicin Olvanil and Glnvamentioning

confidence: 99%

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The Responses of Rat Trigeminal Ganglion Neurons to Capsaicin and Two Nonpungent Vanilloid Receptor Agonists, Olvanil and Glyceryl Nonamide

Liu

Chen

et al. 1997

J. Neurosci.

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Capsaicin, the pungent ingredient in hot pepper, activates and subsequently desensitizes a subset of polymodal nociceptors. Because its initial application to skin produces pain, nonpungent analogs such as olvanil and glyceryl nonivamide (GLNVA) were synthesized to enhance its clinical use. To explore how these nonpungent analogs differ from capsaicin, whole-cell patch-clamp recordings were performed on cultured rat trigeminal ganglion neurons.In neurons held at Ϫ60 mV, capsaicin, olvanil, and GLNVA were found to activate one or two kinetically distinct inward currents. Two inward currents were also activated when extracellular Ca 2ϩ was replaced with Ba 2ϩ and also when intracellular chloride was replaced by aspartate. The reversal potentials of the rapidly and slowly activating currents were 15.3 Ϯ 6 and Ϫ4.0 Ϯ 2.5 mV, respectively. These data provide strong evidence for subtypes of vanilloid receptors. One difference among these agonists is that, on average, the activation kinetics of the currents evoked by 1 M olvanil and 30 M GLNVA are considerably slower than those evoked by 1 M capsaicin. Measurements of the peak current, Ip, versus agonist concentration were fit to the Hill equation to yield values of the half maximal concentrations (K 1/2 ), and the Hill coefficients (n). For capsaicin, olvanil, and GLNVA, K 1/2 ϭ 0.68, 0.59, and 27.0 M; and n ϭ 1.38, 1.32, and 1.24, respectively.We propose that olvanil and GLNVA are nonpungent because they activate different subtypes of receptors and/or because of their activation kinetics (compared with capsaicin) are, on average, slower than the rate they inhibit action potentials from polymodal nociceptors. Key words: pain; taste; vanilloid receptors; pungent; olvanil; capsaicinCapsaicin, the pungent ingredient in chili pepper, produces pain and inflammation when placed on skin or mucus membranes (Holzer, 1991;Szolcanyi et al., 1991). These effects result from the activation of cation-selective channels in polymodal nociceptors causing peptides and transmitters to be released from their peripheral and central terminals. The selectivity of capsaicin for polymodal nociceptors, coupled with the fact that on repeated applications it produces a long-lasting desensitization of these neurons, has made it useful clinically as an anti-nociceptive and -inflammatory compound. a One disadvantage of using capsaicin clinically is that its initial contact with skin produces marked pain and inflammation that sometimes prevents continuance. To reduce these initial responses, protocols were developed in which the capsaicin concentration, the interstimulus interval, and the delivery vehicle were varied systematically (Craft and Porreca, 1992). Another approach was to synthesize analogs of capsaicin with properties that will not cause marked pain on the initial application. This latter approach has followed the pioneering structure activity work of Szolcsanyi and Jansco-Gabor (1975a,b), who found that analogs with longer acyl chains or with altered phenolic hydroxy groups were less pun...

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Section: Currents Activated By Capsaicin Olvanil and Glnvamentioning

confidence: 69%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Currents Activated By Capsaicin Olvanil and Glnvamentioning

confidence: 99%

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The Responses of Rat Trigeminal Ganglion Neurons to Capsaicin and Two Nonpungent Vanilloid Receptor Agonists, Olvanil and Glyceryl Nonamide

Liu

Chen

et al. 1997

J. Neurosci.

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“…This, combined with the effects of pronounced desensitisation exhibited by the TG neurone preparation (Liu & Simon, 1996a), may have confounded the ability to identify this interesting aspect of piperine pharmacology. We must note, however, that it is also equally plausible that TRPV1 receptors in the trigeminal ganglia may differ from those in recombinant and DRG preparations as has been previously suggested to explain differences in the pharmacology of capsazepine and indeed capsaicin (Liu & Simon, 1996b). We cannot currently explain why piperine, a structurally similar molecule to capsaicin (Figure 1a), which is thought to act at the same site on the receptor (as defined by displacement of [ 3 H]Resiniferatoxin, Szallasi & Blumberg, 1991), should show this greater efficacy.…”

Section: Fn Mcnamara Et Al Effects Of Piperine At Trpv1mentioning

confidence: 88%

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

McNamara

Randall

Gunthorpe

2005

British J Pharmacology

273

186

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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 (2574-fold between À70 and þ 70 mV) and a reversal potential of 0.070.4 mV, which was indistinguishable from that of the prototypical TRPV1 agonist capsaicin. 4 Although piperine was a less potent agonist (EC 50 ¼ 37.971.9 mM) than capsaicin (EC 50 ¼ 0.2970.05 mM), 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 (230720%, n ¼ 11) or capsaicin (284732%, n ¼ 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 ¼ 9.970.7 s) than capsaicin (t 1/2 420 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.

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Vanilloid Receptor Pathways

Tominaga

2007

Handbook of Contemporary Neuropharmacology

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Capsaicin receptor, TRPV1, is a nociceptor‐specific ion channel that can be activated not only by capsaicin but also by noxious heat (with a thermal threshold >43°) or protons (acidification), all of which are known to cause pain in vivo. The studies using TRPV1‐deficient mice have shown that TRPV1 is essential for selective modalities of pain sensation and for thermal hyperalgesia induced by tissue injury. Sensitization of TRPV1 through its phosphorylation revealed the involvement of TRPV1 in inflammatory pain. Given the fact that TRPV1 is a key molecule in peripheral nociception, modulation of TRPV1 function will lead to the development of novel anti‐nociceptive or anti‐inflammatory agents.

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Capsaicin-induced currents with distinct desensitization and Ca2+ dependence in rat trigeminal ganglion cells

Cited by 167 publications

References 0 publications

The Responses of Rat Trigeminal Ganglion Neurons to Capsaicin and Two Nonpungent Vanilloid Receptor Agonists, Olvanil and Glyceryl Nonamide

The Responses of Rat Trigeminal Ganglion Neurons to Capsaicin and Two Nonpungent Vanilloid Receptor Agonists, Olvanil and Glyceryl Nonamide

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

Vanilloid Receptor Pathways

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