Expression of TAS2R14 in the intestinal endocrine cells of non-human primates

Abstract

Background

Recent studies have demonstrated that genes related to bitter taste receptors (TAS2Rs) on various chromosomes are expressed in extra-oral organs of various animals. The bitter taste receptor TAS2R14 is conserved among primate species and shows broad ligand sensitivity. Mice have a number of orthologues to primate TAS2R14 located in tandem on chromosome 16; however, their expression patterns are not unique.

Objective

We characterized the expression of TAS2R14 in various cell types in the intestines of the rhesus macaque and evaluated its role in hormone production in the gut.

Methods

TAS2R14 expression was examined in the intestines of rhesus macaques, a common non-human primate model, by RT-qPCR and immunohistochemical staining.

Results

Mean expression levels of TAS2R14 in the duodenum, ileum, and colon were similar to each other and were lower than those in circumvallate papillae. An immunohistochemical analysis revealed TAS2R14 immunoreactivity in enteroendocrine cells positive for cholecystokinin, serotonin, and the G protein GNAT3.

Conclusion

These results suggest that primate TAS2R14 is broadly expressed in the intestine, mainly in enteroendocrine cells, and promotes gut hormone secretion in response to bitter stimuli.

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Abbreviations

T2R:

Bitter taste receptor protein

TAS2R:

Bitter taste receptor gene in primates

Tas2R:

Bitter taste receptor gene in rodents

DAPI:

4′,6-Diamidino-2-phenylindole

GI tract:

Gastrointestinal tract

EEC:

Enteroendocrine cell

EC:

Enterochromaffin

CCK:

Cholecystokinin

5-HT:

Serotonin

References

  1. Alcaino C, Knutson KR, Treichel AJ, Yildiz G, Strege PR, Linden DR, Lic JH, Leiter AB, Szurszewsk JH, Farrugia G, Beyder A (2018) A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release. PNAS 115:E7632–E7641. https://doi.org/10.1073/pnas.1804938115

    CAS  Article  PubMed  Google Scholar 

  2. Behrens M, Meyerhof W (2011) Gustatory and extragustatory functions of mammalian taste receptors. Physiol Behav 105:4–13. https://doi.org/10.1016/j.physbeh.2011.02.010

    CAS  Article  PubMed  Google Scholar 

  3. Behrens M, Born S, Redel U, Voigt N, Schuh V, Raguse JD, Meyerhof W (2012) Immunohistochemical detection of TAS2R38 protein in human taste cells. PLoS ONE 7:e40304

    CAS  Article  Google Scholar 

  4. Braun T, Voland P, Kunz L, Prinz C, Gratzl M (2017) Enterochromaffin cells of the human gut: sensors for spices and odorants. Gastroenterology 132:1890–1901. https://doi.org/10.1053/j.gastro.2007.02.036

    CAS  Article  Google Scholar 

  5. Fakhry J, Wang J, Martins P, Fothergill LJ, Hunne B, Prieur P, Shulkes A, Rehfeld JF, Callaghan B, Furness JB (2017) Distribution and characterisation of CCK containing enteroendocrine cells of the mouse small and large intestine. Cell Tissue Res 369:245–253. https://doi.org/10.1007/s00441-017-2612-1

    CAS  Article  PubMed  Google Scholar 

  6. Goncalves A, Leigh-Brown S, Thybert D, Stefflova K, Turro E, Flicek P, Brazma A, Odom DT, Marioni JC (2012) Extensive compensatory cis-trans regulation in the evolution of mouse gene expression. Genome Res 22:2376–2384. https://doi.org/10.1101/gr.142281.112

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Gu F, Liu X, Liang J, Chen J, Chen F, Li F (2015) Bitter taste receptor mTas2r105 is expressed in small intestinal villus and crypts. Biochem Biophys Res Commun. https://doi.org/10.1016/j.bbrc.2015.06.038

    Article  PubMed  Google Scholar 

  8. Imai H, Hakukawa M, Hayashi M, Iwatsuki K, Masuda K (2020) Expression of bitter taste receptors in the intestinal cells of non-human primates. Int J Mol Sci 21:902. https://doi.org/10.3390/ijms21030902

    CAS  Article  PubMed Central  Google Scholar 

  9. Jeon T-I, Zhu B, Larson JL, Osborne TF (2008) SREBP-2 regulates gut peptide secretion through intestinal bitter taste receptor signaling in mice. J Clin Invest 118:3693–3700. https://doi.org/10.1172/JCI36461

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Kim K-S, Egan JM, Jang H-J (2014) Denatonium induces secretion of glucagon-like peptide-1 through activation of bitter taste receptor pathways. Diabetologia 57:2117–2125. https://doi.org/10.1007/s00125-014-3326-5

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Le Nevé B, Foltz M, Daniel H, Gouka R (2010) The steroid glycoside H.g.-12 from Hoodia gordonii activates the human bitter receptor TAS2R14 and induces CCK release from HuTu-80 cells. Am J Physiol Gastrointest Liver Physiol 299:G1368–G1375. https://doi.org/10.1152/ajpgi.00135.2010

    CAS  Article  PubMed  Google Scholar 

  12. Lu P, Zhang C-H, Lifshitz LM, ZhuGe R (2017) Extraoral bitter taste receptors in health and disease. J Gen Physiol 149:181–197. https://doi.org/10.1085/jgp.201611637

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Lund ML, Egerod KL, Engelstoft MS, Dmytriyeva O, Theodorsson E, Patel BA, Schwartz TW (2018) Enterochromaffin 5-HT cells. A major target for GLP-1 and gut microbial metabolites. Mol Metab 11:7083. https://doi.org/10.1016/j.molmet.2018.03.004

    CAS  Article  Google Scholar 

  14. Luo XC, Chen ZH, Xue JB, Zhao DX, Lu C, Li YH, Li SM, Du YW, Liu Q, Wang P, Huang LM (2019) Infection by the parasitic helminth Trichinella spiralis activates a Tas2r-mediated signaling pathway in intestinal tuft cells. Proc Natl Acad Sci USA 116:5564–5569. https://doi.org/10.1073/pnas.1812901116

    CAS  Article  PubMed  Google Scholar 

  15. Martins P, Fakhry J, de Oliveira EC, Hunne B, Fothergill LJ, Ringuet M, Reis DA, Rehfeld JF, Callaghan B, Furness JB (2017) Analysis of enteroendocrine cell populations in the human colon. Cell Tissue Res 367:161–168. https://doi.org/10.1007/s00441-016-2530-7

    CAS  Article  PubMed  Google Scholar 

  16. Meyerhof W, Batram C, Kuhn C, Brockhoff A, Chudoba E, Bufe B, Appendino G, Behrens M (2010) The molecular receptive ranges of human TAS2R bitter taste receptors. Chem Senses 35:157–170. https://doi.org/10.1093/chemse/bjp092

    CAS  Article  PubMed  Google Scholar 

  17. Prandi S, Voigt A, Meyerhof W, Behrens M (2018) Expression profiling of Tas2r genes reveals a complex pattern along the mouse GI tract and the presence of Tas2r131 in a subset of intestinal Paneth cells. Cell Mol Life Sci 75:49–65. https://doi.org/10.1007/s00018-017-2621-y

    CAS  Article  PubMed  Google Scholar 

  18. Simon R, Foster SR, Enzo R, Porrello ER, Purdue B, Chan H-W, Voigt A, Frenzel S, Ross D, Hannan RD, Moritz KM, David G, Simmons DG, Molenaar P, Roura E, Boehm U, Meyerhof W, Thomas WG (2013) Expression, regulation, and putative nutrient-sensing function of taste GPCRs in the heart. PLoS ONE 8:e64579. https://doi.org/10.1371/journal.pone.0064579

    CAS  Article  Google Scholar 

  19. Vegezzi G, Anselmi L, Huynh J, Barocelli E, Rozengurt E, Raybould H, Sternini C (2014) Diet-induced regulation of bitter taste receptor subtypes in the mouse gastrointestinal tract. PLoS ONE 9:e107732. https://doi.org/10.1371/journal.pone.0107732

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Xie C, Wang X, Young RL, Horowitz M, Rayner CK, Wu T (2018) Role of intestinal bitter sensing in enteroendocrine hormone secretion and metabolic control. Front Endocrinol (Lausanne) 9:576. https://doi.org/10.3389/fendo.2018.00576

    Article  Google Scholar 

  21. Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Hsiao MSK (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161:264–276. https://doi.org/10.1016/j.cell.2015.02.047

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Ye L, Mueller O, Bagwell J, Bagnat M, Liddle RA, John F, Rawls JF (2019) High fat diet induces microbiota-dependent silencing of enteroendocrine cells. eLife 8:e48479. https://doi.org/10.7554/eLife.48479

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank Drs. Yoshiro Ishimaru, Takumi Misaka, and Keiko Abe and Hiroaki Matsunami for providing HEK293T cells. We also wish to express our gratitude to the members of the molecular biology section of the Primate Research Institute, Kyoto University. This work was supported by the Cooperative Research Program of the Primate Research Institute, Kyoto University (R2-A1). This research was funded by Grants-in-Aid from the Japan Society for the Promotion of Science (KAKENHI 19K21586 and 18H04005 to H.I.), and research grants from the Kobayashi International Scholarship Foundation, the Terumo Foundation for Life Sciences and Arts, the Umami Manufacturers Association of Japan, and the JSPS and DG-RSTHE or NSF under the Japan-Indonesia or Korea Research Cooperative Program and Core-to-Core Program to H.I.

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Correspondence to Hiroo Imai or Katsuyoshi Masuda.

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Hayashi, M., Inaba, A., Hakukawa, M. et al. Expression of TAS2R14 in the intestinal endocrine cells of non-human primates. Genes Genom 43, 259–267 (2021). https://doi.org/10.1007/s13258-021-01054-7

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Keywords

  • TAS2R14
  • Enteroendocrine
  • CCK
  • 5-HT
  • Non-human primates