Abstract
The transient receptor potential (TRP) channel superfamily is a set of channel genes that mediate numerous physiological functions such as sensing irritants or detecting temperature changes. Despite their functions, expressional information on TRP channels in various organs is largely elusive. Therefore, we conducted a systematic quantitative comparison of each mRNA expression level of 22 mouse TRP channels in various organs. As a result, we found that average levels of TRP channel transcripts were very low reaching ∼3% of the GAPDH transcript level. Among 22 TRP channels, TRPC1 and TRPM7 were most abundant in the majority of organs. In contrast, TRPV3, TRPV5, TRPV6, TRPC7, TRPM1, and TRPM5 elicited very low message profiles throughout the major organs. Consistent with their functions as molecular sensors for irritants and temperature changes, TRPV1, TRPM8 and TRPA1 showed exclusive expression in sensory ganglia. TRPC3 and TRPM3 were abundant in the sensory ganglia and brain. High levels of transcripts of TRPV2, TRPC6, TRPM4, and TRPM6 were observed in the lung. In addition, channel transcript levels were very low except TRPM7 in the liver. In summary, the expression profile of TRP channels in major tissues provides insight to their physiological functions and therefore application to new drug development.
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Bandell, M., Story, G. M., Hwang, S. W., Viswanath, V., Eid, S. R., Petrus, M. J., Earley, T. J., and Patapoutian, A., Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron, 41, 849–857 (2004).
Bang, S., Yoo, S., Oh, U., and Hwang, S. W., Endogenous lipidderived ligands for sensory TRP ion channels and their pain modulation. Arch. Pharm. Res., 33, 1509–1520 (2010).
Bautista, D. M., Jordt, S. E., Nikai, T., Tsuruda, P. R., Read, A. J., Poblete, J., Yamoah, E. N., Basbaum, A. I., and Julius, D., TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell, 124, 1269–1282 (2006).
Caterina, M. J., Rosen, T. A., Tominaga, M., Brake, A. J., and Julius, D., A capsaicin-receptor homologue with a high threshold for noxious heat. Nature, 398, 436–441 (1999).
Caterina, M. J., Schumacher, M. A., Tominaga, M., Rosen, T. A., Levine, J. D., and Julius, D., The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature, 389, 816–824 (1997).
Cho, Y., Jang, Y., Yang, Y. D., Lee, C. H., Lee, Y., and Oh, U., TRPM8 mediates cold and menthol allergies associated with mast cell activation. Cell Calcium, 48, 202–208 (2010).
Dadon, D. and Minke, B., Cellular functions of transient receptor potential channels. Int. J. Biochem. Cell Biol., 42, 1430–1445 (2010).
Fonfria, E., Murdock, P. R., Cusdin, F. S., Benham, C. D., Kelsell, R. E., and Mcnulty, S., Tissue distribution profiles of the human TRPM cation channel family. J. Recept. Signal Transduct. Res., 26, 159–178 (2006).
Guibert, C., Ducret, T., and Savineau, J. P., Expression and physiological roles of TRP channels in smooth muscle cells. Adv. Exp. Med. Biol., 704, 687–706 (2011).
Guler, A. D., Lee, H., Iida, T., Shimizu, I., Tominaga, M., and Caterina, M., Heat-evoked activation of the ion channel, TRPV4. J. Neurosci., 22, 6408–6414 (2002).
Hardie, R. C. and Minke, B., The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors. Neuron, 8, 643–651 (1992).
Jang, Y., Jung, J., Kim, H., Oh, J., Jeon, J. H., Jung, S., Kim, K. T., Cho, H., Yang, D. J., Kim, S. M., Kim, I. B., Song, M. R., and Oh, U., Axonal neuropathy-associated TRPV4 regulates neurotrophic factor-derived axonal growth. J. Biol. Chem., 287, 6014–6024 (2012).
Kunert-Keil, C., Bisping, F., Kruger, J., and Brinkmeier, H., Tissue-specific expression of TRP channel genes in the mouse and its variation in three different mouse strains. BMC Genomics, 7, 159 (2006).
Kwan, K. Y., Allchorne, A. J., Vollrath, M. A., Christensen, A. P., Zhang, D. S., Woolf, C. J., and Corey, D. P., TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron, 50, 277–289 (2006).
Lee, S. Y., Lee, J. H., Kang, K. K., Hwang, S. Y., Choi, K. D., and Oh, U., Sensitization of vanilloid receptor involves an increase in the phosphorylated form of the channel. Arch. Pharm. Res., 28, 405–412 (2005).
Liedtke, W., Choe, Y., Marti-Renom, M. A., Bell, A. M., Denis, C. S., Sali, A., Hudspeth, A. J., Friedman, J. M., and Heller, S., Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell, 103, 525–535 (2000).
Liedtke, W. and Friedman, J. M., Abnormal osmotic regulation in trpv4-/-mice. Proc. Natl. Acad. Sci. U. S. A., 100, 13698–13703 (2003).
Lucas, P., Ukhanov, K., Leinders-Zufall, T., and Zufall, F., A diacylglycerol-gated cation channel in vomeronasal neuron dendrites is impaired in TRPC2 mutant mice: mechanism of pheromone transduction. Neuron, 40, 551–561 (2003).
Maroto, R., Raso, A., Wood, T. G., Kurosky, A., Martinac, B., and Hamill, O. P., TRPC1 forms the stretch-activated cation channel in vertebrate cells. Nat. Cell Biol., 7, 179–185 (2005).
Mckemy, D. D., Neuhausser, W. M., and Julius, D., Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature, 416, 52–58 (2002).
Okada, T., Inoue, R., Yamazaki, K., Maeda, A., Kurosaki, T., Yamakuni, T., Tanaka, I., Shimizu, S., Ikenaka, K., Imoto, K., and Mori, Y., Molecular and functional characterization of a novel mouse transient receptor potential protein homologue TRP7. Ca(2+)-permeable cation channel that is constitutively activated and enhanced by stimulation of G protein-coupled receptor. J. Biol. Chem., 274, 27359–27370 (1999).
Park, U., Vastani, N., Guan, Y., Raja, S. N., Koltzenburg, M., and Caterina, M. J., TRP vanilloid 2 knock-out mice are susceptible to perinatal lethality but display normal thermal and mechanical nociception. J. Neurosci., 31, 11425–11436 (2011).
Peier, A. M., Moqrich, A., Hergarden, A. C., Reeve, A. J., Andersson, D. A., Story, G. M., Earley, T. J., Dragoni, I., Mcintyre, P., Bevan, S., and Patapoutian, A., A TRP channel that senses cold stimuli and menthol. Cell, 108, 705–715 (2002).
Pfaffl, M. W., A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res., 29, e45 (2001).
Riccio, A., Medhurst, A. D., Mattei, C., Kelsell, R. E., Calver, A. R., Randall, A. D., Benham, C. D., and Pangalos, M. N., mRNA distribution analysis of human TRPC family in CNS and peripheral tissues. Brain Res. Mol. Brain Res., 109, 95–104 (2002).
Ririe, K. M., Rasmussen, R. P., and Wittwer, C. T., Product differentiation by analysis of DNA melting curves during the polymerase chain reaction. Anal. Biochem., 245, 154–160 (1997).
Runnels, L. W., Yue, L., and Clapham, D. E., TRP-PLIK, a bifunctional protein with kinase and ion channel activities. Science, 291, 1043–1047 (2001).
Shapovalov, G., Lehen’kyi, V., Skryma, R., and Prevarskaya, N., TRP channels in cell survival and cell death in normal and transformed cells. Cell Calcium, 50, 295–302 (2011).
Shin, J., Cho, H., Hwang, S. W., Jung, J., Shin, C. Y., Lee, S. Y., Kim, S. H., Lee, M. G., Choi, Y. H., Kim, J., Haber, N. A., Reichling, D. B., Khasar, S., Levine, J. D., and Oh, U., Bradykinin-12-lipoxygenase-VR1 signaling pathway for inflammatory hyperalgesia. Proc. Natl. Acad. Sci. U. S. A., 99, 10150–10155 (2002).
Smith, G. D., Gunthorpe, M. J., Kelsell, R. E., Hayes, P. D., Reilly, P., Facer, P., Wright, J. E., Jerman, J. C., Walhin, J. P., Ooi, L., Egerton, J., Charles, K. J., Smart, D., Randall, A. D., Anand, P., and Davis, J. B., TRPV3 is a temperaturesensitive vanilloid receptor-like protein. Nature, 418, 186–190 (2002).
Staaf, S., Franck, M. C., Marmigere, F., Mattsson, J. P., and Ernfors, P., Dynamic expression of the TRPM subgroup of ion channels in developing mouse sensory neurons. Gene Expr. Patterns, 10, 65–74 (2010).
Sulk, M., Seeliger, S., Aubert, J., Schwab, V. D., Cevikbas, F., Rivier, M., Nowak, P., Voegel, J. J., Buddenkotte, J., and Steinhoff, M., Distribution and expression of nonneuronal transient receptor potential (TRPV) ion channels in rosacea. J. Invest. Dermatol., 132, 1253–1262 (2012).
Vay, L., Gu, C., and Mcnaughton, P. A., The thermo-TRP ion channel family: properties and therapeutic implications. Br. J. Pharmacol., 165, 787–801 (2012).
Vriens, J., Owsianik, G., Hofmann, T., Philipp, S. E., Stab, J., Chen, X., Benoit, M., Xue, F., Janssens, A., Kerselaers, S., Oberwinkler, J., Vennekens, R., Gudermann, T., Nilius, B., and Voets, T., TRPM3 is a nociceptor channel involved in the detection of noxious heat. Neuron, 70, 482–494 (2011).
Wang, X. and Seed, B., A PCR primer bank for quantitative gene expression analysis. Nucleic Acids Res., 31, e154 (2003).
Wu, L. J., Sweet, T. B., and Clapham, D. E., International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family. Pharmacol. Rev., 62, 381–404 (2010).
Xu, H., Ramsey, I. S., Kotecha, S. A., Moran, M. M., Chong, J. A., Lawson, D., Ge, P., Lilly, J., Silos-Santiago, I., Xie, Y., Distefano, P. S., Curtis, R., and Clapham, D. E., TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature, 418, 181–186 (2002).
Yu, Y., Fantozzi, I., Remillard, C. V., Landsberg, J. W., Kunichika, N., Platoshyn, O., Tigno, D. D., Thistlethwaite, P. A., Rubin, L. J., and Yuan, J. X., Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. Proc. Natl. Acad. Sci. U. S. A., 101, 13861–13866 (2004).
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Jang, Y., Lee, Y., Kim, S.M. et al. Quantitative analysis of TRP channel genes in mouse organs. Arch. Pharm. Res. 35, 1823–1830 (2012). https://doi.org/10.1007/s12272-012-1016-8
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DOI: https://doi.org/10.1007/s12272-012-1016-8