Chemical Senses Vol. 30 No. suppl 1 © Oxford University
Press 2005; all rights reserved
Gustatory Effects of Capsaicin that are Independent of TRPV1 Receptors
1 Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA and 2 Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA
Correspondence to be sent to: Rui M. Costa, e-mail: costa{at}neuro.duke.edu
Key words: capsaicin, multimodal, taste, TRC, TRPV1
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Introduction |
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 Top Introduction Materials and MethodsResultsDiscussionAcknowledgementsReferences |
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In order to choose which foods are palatable and safe to ingest, it is important to integrate information from different modalities, not only chemosensory (taste and olfaction), but also somatosensory (texture, irritation, nociception) (Scott and Verhagen, 2000
). Capsaicin, the
pungent component from chili peppers, has been shown to alter taste perception
(Lawless and Stevens, 1984;
Prescott and Stevenson, 1995;
Simons et al., 2002) and has
traditionally been added to foods to change their palatability. The effects of capsaicin
on taste could emerge from the integration throughout the gustatory axis of information
originating from capsaicin’s direct effects on taste receptor cells (TRCs)
(Liu and Simon, 2001;
Park et al., 2003;
Lyall et al., 2004) and/or
from information resulting from the effects of capsaicin on TRPV1 receptors in trigeminal
nerve endings in the mouth (Liu and Simon,
1996, 2000). Recent studies have shown that capsaicin can alter neural
responses to tastants at the level of the nucleus tractus solitarius (NTS) and that these
effects seem to be independent of trigeminal transmission (Simons et al., 2003). Previously,
Okuni (1977) showed that chorda
tympani fibers can be activated by capsaicin, indicating capsaicin can affect the
gustatory pathway and more recently,
Lyall et al. (2004)
presented evidence for a TRPV1 splice variant in TRCs that is responsible for the
amiloride-insensitive responses to salts. Here, we found that in dissociated rat TRCs
capsaicin inhibits voltage-gated inward and outward currents. Furthermore, we found that
in TRPV1–/– mice capsaicin can alter taste
preference to sucrose. These results demonstrate that the effects of capsaicin in taste
perception do not result exclusively from the activation of capsaicin-sensitive
receptors, but also through non-specific TRPV1-independent mechanisms. |
Materials and Methods |
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TopIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
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Taste Preference
All procedures were approved by Duke IACUC.
TRPV1–/– mice—WT and congenic
TRPV1–/– littermates in the C57/B6J
genetic background, males and female, age 3–7 months—were the generous gift
from Dr David Julius and were previously described (Caterina et al., 2000).
Mice were water restricted and habituated to drink for 1 h/day (4 days) from two tubes with sippers; one containing water and the other 100 mM sucrose. To test for taste preference (sucrose/water + sucrose) of the TRPV1–/– mice in the presence of capsaicin, the solutions consisted of water, 1% DMSO, 100 µM capsaicin and 100 mM sucrose, 1% DMSO, 100 µM capsaicin. As controls, the solutions consisted only of water with 1% DMSO and 100 mM sucrose with 1% DMSO. The relative position of the sucrose and water tubes in the cage (right or left) varied from day to day, and every condition (with or without capsaicin) was tested twice in each side (right or left) and the results for each side averaged. Two independent groups, totaling 13 TRPV1–/– mice, were used to study the effects of capsaicin on taste preference.
Isolation of TRCs and Electrophysiology
TRCs from rat circumvallate papillae were isolated as previously described (Herness et al., 1997). The isolated
taste buds were gently triturated to obtain individual TRCs that were plated into the
recording chamber. Whole cell patch clamp experiments were done as described (Liu et al., 2001). In all the TRCs
tested, 30 µM capsaicin did not activate an inward current when the cells were held
at a potential of –60 mV. The peak current-voltage (Ip-V) relationship was
determined using a voltage step protocol in which the voltage was increased in 10 mV step
increments from the holding potential of –60mV to test potentials up to 80mV. Peak
currents were analyzed using pCLAMP software and plotted against the applied voltage to
obtain the Ip-V relations.
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Results |
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TopIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
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Capsaicin inhibits inward and outward currents in isolated taste cells
Figure
1 shows that that the application of
30 µM capsaicin inhibited both the voltage-dependent inward and outward currents.
Also shown is that the currents are largely reversible after a 4 min washout. On average,
30 µM capsaicin inhibited the peak inward currents 20 ± 3%
(n = 6) and the steady state outward currents 31 ± 4%
(n = 6) The inward currents are voltage-gated sodium and calcium currents
and the outward current primarily reflects a delayed rectifier potassium current
(Zhao et al., 2002).
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Capsaicin alters taste preference in TRPV1–/– mice
The results from electrophysiological recordings suggest that capsaicin can affect inward and outward currents in TRCs in a non-specific manner. We therefore tested, using a two-bottle preference test, whether taste preference would be affected by capsaicin in mice that lack TRPV1 receptors. We verified that deletion of TRPV1 per se did not affect preference for sucrose as TRPV1–/– mice showed the same preference for sucrose as their WT littermates [t(9) = 1.59, P > 0.05, data not shown]. Additionally, while WT mice refused to drink any solution containing 100 µM capsaicin, TRPV1–/– mice consumed the same amount of liquid in the presence or absence of 100 µM capsaicin [t(12) = 0.28, P > 0.05, P > 0.05; Figure 2B]. However, the preference of TRPV1–/– mice for 100 mM sucrose was decreased in the presence of 100 µM capsaicin. That is, whereas in the absence of capsaicin TRPV1–/– mice displayed a clear preference for 100 mM sucrose [right DMSO t(12) = 3.41, P < 0.05; left DMSO t(12) = 2.89, P < 0.05], in the presence of 100 µM capsaicin they failed to show that preference [right capsaicin t(12) = 0.89, P > 0.05; left capsaicin t(12) = 1.27, P > 0.05; Figure 2A]. Furthermore, TRPV1–/– mice exhibited a preference index that was significantly lower in the presence than in the absence of capsaicin [t(12) = 2.89, P < 0.05; Figure 2A]. This effect was repeatable (see Materials and methods) and independent of the relative side of placement of the sucrose bottle (right or left), indicating that indeed capsaicin could affect taste preference in TRPV1–/– mice.
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Discussion |
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TopIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
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In this study we showed that capsaicin could inhibit voltage-gated inward and outward currents in TRCs in a non-specific manner that is similar to the way it does it does in sensory trigeminal neurons (Liu et al., 2001
;
Liu and Simon, 2003). These
voltage-gated currents have been shown to be important in several aspects of gustatory
physiology (Herness and Gilbertson,
1999). We also showed that capsaicin can affect taste perception in
TRPV1–/– mice. Taken together, these results
suggest that the effects of capsaicin may affect taste perception not exclusively via the
activation of capsaicin-sensitive receptors, but also via a direct, non-specific and
TRPV1-independent effect of capsaicin in TRCs.
Being a non-polar compound, capsaicin can partition into the acyl chain region of the
plasma membrane where it can alter its material properties, thereby altering channel
(including sodium channel) function (Lundbaek
et al., 2004) or even possibly TRPM5, receptors.
Similarly it can also partition into the cytoplasm where it can affect the function of
GPCRs, including those associated with taste (Peri et al., 2000). Another possibility is that
capsaicin can act on alternative receptors in TRCs. A recent study has shown that a TRPV1
variant is expressed in TRCs (Lyall et
al., 2004). Although this variant could be responsible for some the
effects of capsaicin in salt taste, it could still not explain capsaicin’s
inhibitory effects on taste preference for sucrose in
TRPV1–/– mice (Figure
2). In summary, capsaicin can evoke a
variety of effects on taste—it can produce a burning sensation, be involved in salt
taste and diminish sweet taste. Which of these myriad of effects it will produce will
depend on the concentration, time of application and presence of capsaicin-sensitive
receptors (Caterina et al.,
2000;
Jordt et al., 2004).
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Acknowledgements |
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TopIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
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This work was supported by funding from the PMERP and the Portuguese FCT to R.M.C. and from PMERP to S.A.S.
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References |
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TopIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
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Caterina, M.J., Leffler, A., Malmberg, A.B., Martin, W.J., Trafton, J., Petersen-Zeitz, K.R., Koltzenburg, M., Basbaum, A.I. and Julius, D. (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science, 288, 306–313.
Herness, M.S. and Gilbertson, T.A. (1999) Cellular mechanisms of taste transduction. Annu. Rev. Physiol., 61, 873–900.[CrossRef][ISI][Medline]
Herness, M.S., Sun, X.D. and Chen, Y. (1997) cAMP and forskolin inhibit potassium currents in rat taste receptor cells by different mechanisms. Am. J. Physiol., 272, C2005–C2018.
Jordt, S.E., Bautista, D.M., Chuang, H.H., McKemy, D.D., Zygmunt, P.M., Hogestatt, E.D., Meng, I.D. and Julius, D. (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature, 427, 260–265.[CrossRef][Medline]
Lawless, H. and Stevens, D.A. (1984) Effects of oral chemical irritation on taste. Physiol. Behav., 32, 995–998.[CrossRef][Medline]
Liu, L. and Simon, S.A. (1996) Capsaicin and nicotine both activate a subset of rat trigeminal ganglion neurons. Am. J. Physiol., 270, C1807–C1814.
Liu, L. and Simon, S.A. (2000) Capsaicin, acid and heat-evoked currents in rat trigeminal ganglion neurons: relationship to functional VR1 receptors. Physiol. Behav., 69, 363–378.[CrossRef][Medline]
Liu, L. and Simon, S.A. (2001) Acidic stimuli activates two distinct pathways in taste receptor cells from rat fungiform papillae. Brain Res., 923, 58–70.[CrossRef][ISI][Medline]
Liu, L. and Simon, S.A. (2003) Modulation of IA currents by capsaicin in rat trigeminal ganglion neurons. J. Neurophysiol., 89, 1387–1401.
Liu, L., Oortgiesen, M., Li, L. and Simon, S.A. (2001) Capsaicin inhibits activation of voltage-gated sodium currents in capsaicin-sensitive trigeminal ganglion neurons. J. Neurophysiol., 85, 745–758.
Lundbaek, J.A., Birn, P., Hansen, A.J., Sogaard, R., Nielsen, C., Girshman, J., Bruno, M.J., Tape, S.E., Egebjerg, J., Greathouse, D.V., Mattice, G.L., Koeppe, R.E. 2nd and Anderson, O.S. (2004) Regulation of sodium channel function by bilayer elasticity: the importance of hydrophobic coupling. Effects of micelle-forming amphiphiles and cholesterol. J. Gen. Physiol., 123, 599–621.
Lyall, V., Heck, G.L., Vinnikova, A.K., Ghosh, S., Phan, T.H., Alam, R.I., Russell, O.F., Malik, S.A., Bigbee, J.W. and DeSimone, J.A. (2004) The mammalian amiloride-insensitive non-specific salt taste receptor is a vanilloid receptor-1 variant. J. Physiol., 558, 147–159.
Okuni, Y. (1977) Response of chorda tympani fibers of the rat to pungent spices and irritants in pungent spices. Shikwa Gakuho, 77, 1323–1349 [in Japanese].[Medline]
Park, K., Brown, P.D., Kim, Y.B. and Kim, J.S. (2003) Capsaicin modulates K+ currents from dissociated rat taste receptor cells. Brain Res., 962, 135–143.[CrossRef][ISI][Medline]
Peri, I., Mamrud-Brains, H., Rodin, S., Krizhanovsky, V., Shai, Y., Nir, S. and Naim, M. (2000) Rapid entry of bitter and sweet tastants into liposomes and taste cells: implications for signal transduction. Am. J. Physiol. Cell. Physiol., 278, C17–C25.
Prescott, J. and Stevenson, R.J. (1995) Effects of oral chemical irritation on tastes and flavors in frequent and infrequent users of chili. Physiol. Behav., 58, 1117–1127.[CrossRef][Medline]
Scott, T.R. and Verhagen, J.V. (2000) Taste as a factor in the management of nutrition. Nutrition, 16, 874–885.[CrossRef][ISI][Medline]
Simons, C.T., O’Mahony, M. and Carstens, E. (2002) Taste suppression following lingual capsaicin pre-treatment in humans. Chem. Senses, 27, 353–365.
Simons, C.T., Boucher, Y. and Carstens, E. (2003) Suppression of central taste transmission by oral capsaicin. J. Neurosci., 23, 978–985.
Zhao, F.L., Lu, S.G. and Herness, S. (2002) Dual actions of caffeine on voltage-dependent currents and intracellular calcium in taste receptor cells. Am. J. Physiol. Regul. Integr. Comp. Physiol., 283, R115–R129.
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