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

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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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

Authors

  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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  5. Toshihide Yokoyama
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  6. Hiroyuki Ito
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Correspondence toHitoshi 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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