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QGP-1 cells release 5-HT via TRPA1 activation; a model of human enterochromaffin cells

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Abstract

Recently, we discovered that transient receptor potential ankyrin1 channel (TRPA1) is highly expressed in human and rat enterochromaffin (EC) cells, and those TRPA1 agonists such as allyl isothiocyanates (AITC) and cinnamaldehyde (CA) enhance the release of serotonin (5-hydroxytryptamine; 5-HT) from EC cells in vitro. In this study, QGP-1 cells, a human pancreatic endocrine cell line, were found to highly express TRPA1 and EC cell marker genes, such as tryptophan hydroxylase 1 (TPH1), chromogranin A (CgA), synaptophysin, ATP-dependent vesicular monoamine transporter 1 (VMAT1), metabotropic glutamate receptor 4 (mGluR4), β1-adrenergic receptor (ADB1), muscarinic 4 acetylcholine receptor (ACM4), substance P, serotonin transporter (SERT), and guanylin. Furthermore, the TRPA1 agonists AITC, CA, and acrolein concentration dependently evoked an increase in intracellular Ca2+ influx and the release of 5-HT in QGP-1 cells. The effects of these TRPA1 agonists were inhibited by ruthenium red, a TRPA1 antagonist, and TRPA1-specific siRNA. These results indicate that the Ca2+ influx increase and 5-HT release induced by AITC, CA and acrolein in QGP-1 cells were mediated by TRPA1, and that the QGP-1 cell line could be a new model for the investigation of TRPA1 function in the human EC cell.

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References

  1. Spiller R (2007) Recent advances in understanding the role of serotonin in gastrointestinal motility in functional bowel disorders: alterations in 5-HT signalling and metabolism in human disease. Neurogastroenterol Motil 19(Suppl 2):25–31. doi:10.1111/j.1365-2982.2007.00965.x

    Article  CAS  PubMed  Google Scholar 

  2. Gershon MD (2003) Plasticity in serotonin control mechanisms in the gut. Curr Opin Pharmacol 3:600–607. doi:10.1016/j.coph.2003.07.005

    Article  CAS  PubMed  Google Scholar 

  3. Gershon MD, Tack J (2007) The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 132:397–414. doi:10.1053/j.gastro.2006.11.002

    Article  CAS  PubMed  Google Scholar 

  4. Platt AJ, Heddle RM, Rake MO, Smedley H (1992) Ondansetron in carcinoid syndrome. Lancet 339:1416. doi:10.1016/0140-6736(92)91235-Z

    Article  CAS  PubMed  Google Scholar 

  5. Crowell MD (2004) Role of serotonin in the pathophysiology of the irritable bowel syndrome. Br J Pharmacol 141:1285–1293. doi:10.1038/sj.bjp.0705762

    Article  CAS  PubMed  Google Scholar 

  6. Jacobsen MB, Hanssen LE, Bratlie J (1992) The effect of somatostatin analogue SMS 201–995 on serotonin levels in the medium of primary carcinoid cell cultures. Scand J Gastroenterol 27:1077–1083. doi:10.3109/00365529209028141

    Article  CAS  PubMed  Google Scholar 

  7. Atkinson W, Lockhart S, Whorwell PJ, Keevil B, Houghton LA (2006) Altered 5-hydroxytryptamine signaling in patients with constipation- and diarrhea-predominant irritable bowel syndrome. Gastroenterology 130:34–43. doi:10.1053/j.gastro.2005.09.031

    Article  CAS  PubMed  Google Scholar 

  8. Modlin IM et al (2008) Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 9:61–72. doi:10.1016/S1470-2045(07)70410-2

    Article  CAS  PubMed  Google Scholar 

  9. Oberg K (2009) Genetics and molecular pathology of neuroendocrine gastrointestinal and pancreatic tumors (gastroenteropancreatic neuroendocrine tumors). Curr Opin Endocrinol Diabetes Obes 16:72–78

    PubMed  Google Scholar 

  10. Kim M, Cooke HJ, Javed NH, Carey HV, Christofi F, Raybould HE (2001) D-glucose releases 5-hydroxytryptamine from human BON cells as a model of enterochromaffin cells. Gastroenterology 121:1400–1406. doi:10.1053/gast.2001.29567

    Article  CAS  PubMed  Google Scholar 

  11. Kidd M, Modlin IM, Eick GN, Champaneria MC (2006) Isolation, functional characterization, and transcriptome of Mastomys ileal enterochromaffin cells. Am J Physiol Gastrointest Liver Physiol 291:G778–G791. doi:10.1152/ajpgi.00552.2005

    Article  CAS  PubMed  Google Scholar 

  12. Van Buren G et al (2007) The development and characterization of a human midgut carcinoid cell line. Clin Cancer Res 13:4704–4712. doi:10.1158/1078-0432.CCR-06-2723

    Article  PubMed  Google Scholar 

  13. Stilling GA et al (2007) Characterization of the functional and growth properties of cell lines established from ileal and rectal carcinoid tumors. Endocr Pathol 18:223–232. doi:10.1007/s12022-007-9001-3

    Article  CAS  PubMed  Google Scholar 

  14. Obata K et al (2005) TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury. J Clin Invest 115:2393–2401. doi:10.1172/JCI25437

    Article  CAS  PubMed  Google Scholar 

  15. Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41:849–857. doi:10.1016/S0896-6273(04)00150-3

    Article  CAS  PubMed  Google Scholar 

  16. Tominaga M, Caterina MJ (2004) Thermosensation and pain. J Neurobiol 61:3–12. doi:10.1002/neu.20079

    Article  PubMed  Google Scholar 

  17. Zhang XF, Chen J, Faltynek CR, Moreland RB, Neelands TR (2008) Transient receptor potential A1 mediates an osmotically activated ion channel. Eur J Neurosci 27:605–611. doi:10.1111/j.1460-9568.2008.06030.x

    Article  PubMed  Google Scholar 

  18. Lee SP, Buber MT, Yang Q, Cerne R, Cortes RY, Sprous DG, Bryant RW (2008) Thymol and related alkyl phenols activate the hTRPA1 channel. Br J Pharmacol 153:1739–1749. doi:10.1038/bjp.2008.85

    Article  CAS  PubMed  Google Scholar 

  19. Bautista DM et al (2006) TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124:1269–1282. doi:10.1016/j.cell.2006.02.023

    Article  CAS  PubMed  Google Scholar 

  20. Story GM et al (2003) ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112:819–829. doi:10.1016/S0092-8674(03)00158-2

    Article  CAS  PubMed  Google Scholar 

  21. Nozawa K et al (2009) TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells. Proc Natl Acad Sci USA 106:3408–3413. doi:10.1073/pnas.0805323106

    Article  CAS  PubMed  Google Scholar 

  22. Stokes A, Wakano C, Koblan-Huberson M, Adra CN, Fleig A, Turner H (2006) TRPA1 is a substrate for de-ubiquitination by the tumor suppressor CYLD. Cell Signal 18:1584–1594. doi:10.1016/j.cellsig.2005.12.009

    Article  CAS  PubMed  Google Scholar 

  23. Kidd M, Eick GN, Modlin IM, Pfragner R, Champaneria MC, Murren J (2007) Further delineation of the continuous human neoplastic enterochromaffin cell line, KRJ-I, and the inhibitory effects of lanreotide and rapamycin. J Mol Endocrinol 38:181–192. doi:10.1677/jme.1.02037

    Article  CAS  PubMed  Google Scholar 

  24. Grube D (1976) The endocrine cells of the gastrointestinal epithelium and the metabolism of biogenic amines in the gastrointestinal tract (author’s transl). Prog Histochem Cytochem 8:1–128

    CAS  PubMed  Google Scholar 

  25. Albano F, de Marco G, Canani RB, Cirillo P, Buccigrossi V, Giannella RA, Guarino A (2005) Guanylin and E. coli heat-stable enterotoxin induce chloride secretion through direct interaction with basolateral compartment of rat and human colonic cells. Pediatr Res 58:159–163. doi:10.1203/01.PDR.0000163380.96434.B9

    Article  CAS  PubMed  Google Scholar 

  26. Iceta R, Mesonero JE, Aramayona JJ, Alcalde AI (2006) Molecular characterization and intracellular regulation of the human serotonin transporter in Caco-2 cells. J Physiol Pharmacol 57:119–130

    CAS  PubMed  Google Scholar 

  27. Gustafsson BI, Bakke I, Tommeras K, Waldum HL (2006) A new method for visualization of gut mucosal cells, describing the enterochromaffin cell in the rat gastrointestinal tract. Scand J Gastroenterol 41:390–395. doi:10.1080/00365520500331281

    Article  PubMed  Google Scholar 

  28. Freeman SL, Bohan D, Darcel N, Raybould HE (2006) Luminal glucose sensing in the rat intestine has characteristics of a sodium-glucose cotransporter. Am J Physiol Gastrointest Liver Physiol 29:G439–G445. doi:10.1152/ajpgi.00079.2006

    Article  Google Scholar 

  29. Zhu JX, Zhu XY, Owyang C, Li Y (2001) Intestinal serotonin acts as a paracrine substance to mediate vagal signal transmission evoked by luminal factors in the rat. J Physiol 530:431–442. doi:10.1111/j.1469-7793.2001.0431k.x

    Article  CAS  PubMed  Google Scholar 

  30. Kidd M, Modlin IM, Gustafsson BI, Drozdov I, Hauso O, Pfragner R (2008) Luminal regulation of normal and neoplastic human EC cell serotonin release is mediated by bile salts, amines, tastants, and olfactants. Am J Physiol Gastrointest Liver Physiol 295:G260–G272. doi:10.1152/ajpgi.00056.2008

    Article  CAS  PubMed  Google Scholar 

  31. Lomax RB, Gallego S, Novalbos J, Garcia AG, Warhurst G (1999) L-Type calcium channels in enterochromaffin cells from guinea pig and human duodenal crypts: an in situ study. Gastroenterology 117:1363–1369. doi:10.1016/S0016-5085(99)70286-6

    Article  CAS  PubMed  Google Scholar 

  32. Andrade EL, Ferreira J, Andre E, Calixto JB (2006) Contractile mechanisms coupled to TRPA1 receptor activation in rat urinary bladder. Biochem Pharmacol 72:104–114. doi:10.1016/j.bcp.2006.04.003

    Article  CAS  PubMed  Google Scholar 

  33. Cecconi D, Donadelli M, Rinalducci S, Zolla L, Scupoli MT, Scarpa A, Palmieri M, Righetti PG (2007) Proteomic analysis of pancreatic endocrine tumor cell lines treated with the histone deacetylase inhibitor trichostatin A. Proteomics 7:1644–1653. doi:10.1002/pmic.200600811

    Article  CAS  PubMed  Google Scholar 

  34. Capurso G et al (2006) Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets. Endocr Relat Cancer 13:541–558. doi:10.1677/erc.1.01153

    Article  CAS  PubMed  Google Scholar 

  35. Siddique ZL, Drozdov I, Floch J, Gustafsson BI, Stunes K, Pfragner R, Kidd M, Modlin IM (2009) KRJ-I and BON cell lines: defining an appropriate enterochromaffin cell neuroendocrine tumor model. Neuroendocrinology 89:458–470. doi:10.1159/000209330

    Google Scholar 

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Acknowledgments

We would like to thank T. Koizumi, M. Yamano, Y. Takinami, R. Takezawa, Y. Takemoto, T. Goto, H. Tanaka, H. Okada, H. Kamada, and M. Okada for their excellent technical assistance and advice.

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Authors and Affiliations

  1. Pharmacology Laboratories, Drug Discovery Research, Astellas Pharma Inc, 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan

    Hitoshi Doihara, Katsura Nozawa, Ryosuke Kojima, Eri Kawabata-Shoda, Toshihide Yokoyama & Hiroyuki Ito

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  1. Hitoshi Doihara
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  2. Katsura Nozawa
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  3. Ryosuke Kojima
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  4. Eri Kawabata-Shoda
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Correspondence to Hitoshi Doihara.

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Hitoshi Doihara and Katsura Nozawa have contributed equally to this work.

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Doihara, H., Nozawa, K., Kojima, R. et al. QGP-1 cells release 5-HT via TRPA1 activation; a model of human enterochromaffin cells. Mol Cell Biochem 331, 239–245 (2009). https://doi.org/10.1007/s11010-009-0165-7

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  • DOI: https://doi.org/10.1007/s11010-009-0165-7

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