title: QGP-1 cells release 5-HT via TRPA1 activation; a model of human enterochromaffin cells.
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), beta1-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 Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Pharmacology Laboratories, Drug Discovery Research, Astellas Pharma Inc, 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan. hitoshi.doihara@jp.astellas.com
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Doihara
authors.forename: Katsura
authors.initials: K
authors.lastname: Nozawa
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kojima
authors.forename: Eri
authors.initials: E
authors.lastname: Kawabata-Shoda
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D001681:Biological Assay; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004759:Enterochromaffin Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D017879:Isothiocyanates / Q000494:pharmacology; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015220:Calcium Channels; D017879:Isothiocyanates; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; D012701:Serotonin; D000171:Acrolein; C004471:allyl isothiocyanate; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase; C012843:cinnamaldehyde; D002118:Calcium