{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T11:32:29Z","timestamp":1781955149815,"version":"3.54.5"},"reference-count":29,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,2,26]],"date-time":"2018-02-26T00:00:00Z","timestamp":1519603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sei-hai-to (TJ-90, Qing Fei Tang), a Chinese traditional medicine, increases ciliary beat frequency (CBF) and ciliary bend angle (CBA) mediated via cAMP (3\u2032,5\u2032-cyclic adenosine monophosphate) accumulation modulated by Ca2+-activated phosphodiesterase 1 (PDE1A). A high concentration of TJ-90 (\u226540 \u03bcg\/mL) induced two types of CBF increases, a transient increase (an initial increase, followed by a decrease) and a sustained increase without any decline, while it only sustained the CBA increase. Upon inhibiting increases in intracellular Ca2+ concentration ([Ca2+]i) by 10 \u03bcM BAPTA-AM (Ca2+-chelator, 1,2-Bis(2-aminophenoxy)ethane-N,N,N\u2032,N\u2032-tetraacetic acid tetrakis(acetoxymethyl ester) or Ca2+\/calmodulin-dependent PDE1 by 8MmIBMX (a selective PDE1 inhibitor), TJ-90 (400 \u03bcg\/mL) induced only the sustained CBF increase without any transient CBF increase. The two types of the CBF increase (the transient increase and the sustained increase) induced by TJ-90 (\u226540 \u03bcg\/mL) were mimicked by the stimulation with both procaterol (100 pM) and ionomycin (500 nM). Thus, TJ-90 stimulates small increases in the intracellular cAMP concentration ([cAMP]i) and [Ca2+]i in airway ciliary cells of mice. These small increases in [cAMP]i and [Ca2+]i cause inducing a transient CBF increase or a sustained CBF increase in an airway ciliary cells, depending on the dominant signal, Ca2+-signal, or cAMP-signal.<\/jats:p>","DOI":"10.3390\/ijms19030658","type":"journal-article","created":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T03:36:12Z","timestamp":1519702572000},"page":"658","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Seihai-to (TJ-90)-Induced Activation of Airway Ciliary Beatings of Mice: Ca2+ Modulation of cAMP-Stimulated Ciliary Beatings via PDE1"],"prefix":"10.3390","volume":"19","author":[{"given":"Haruka","family":"Kogiso","sequence":"first","affiliation":[{"name":"Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Ikeuchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Sumiya","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigekuni","family":"Hosogi","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saori","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, Takatsuki 569-1096 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikao","family":"Shimamoto","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, Takatsuki 569-1096 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Inui","sequence":"additional","affiliation":[{"name":"Saisei Mirai Clinics, Moriguchi 570-0012, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3846-0937","authenticated-orcid":false,"given":"Yoshinori","family":"Marunaka","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"},{"name":"Department of Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"},{"name":"Japan Institute for Food Education and Health, St. Agnes\u2019 University, Kyoto 602-8013, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Nakahari","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"},{"name":"Department of Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"},{"name":"Japan Institute for Food Education and Health, St. Agnes\u2019 University, Kyoto 602-8013, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/path.1652","article-title":"Cilia-related diseases","volume":"204","author":"Afzelius","year":"2004","journal-title":"J. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev.physiol.69.040705.141253","article-title":"Regulation of mammalian ciliary beating","volume":"69","author":"Salathe","year":"2007","journal-title":"Annu. Rev. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1164\/ajrccm.154.6.8970383","article-title":"Mucociliary clearance in the airways","volume":"154","author":"Wanner","year":"1996","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1113\/jphysiol.1996.sp021735","article-title":"Asynmmetric interactions between phosphorylation pathways regulating ciliary beat frequency in human nasal respiratory epithelium in vitro","volume":"496","author":"Smith","year":"1996","journal-title":"J. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0944-7113(99)80042-7","article-title":"Effects of quing Fei Tang (TJ-90) on aspiration pneumonia in mice","volume":"6","author":"Iwasaki","year":"1999","journal-title":"Phytomedicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1078\/0944-7113-00111","article-title":"Effects of Seihai-to, a Kampo medicine, in relapsing aspiration pneumonia\u2014An open-label pilot study","volume":"9","author":"Mantani","year":"2002","journal-title":"Phytomedicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1348-0421.1982.tb00207.x","article-title":"Interferon induction by glycyrrhizin and glycyrrhetinic acid in mice","volume":"26","author":"Abe","year":"1982","journal-title":"Microbiol. Immunol."},{"key":"ref_8","first-page":"190","article-title":"Effects of gomishin A on IL4 and 6 production from human peripheral blood mononuclear cells","volume":"7","author":"Hasegawa","year":"1990","journal-title":"J. Tradit. Med."},{"key":"ref_9","first-page":"1210","article-title":"Effects of Sei-hai-to on iontransport in airway epithelial cells","volume":"43","author":"Chiyotani","year":"1994","journal-title":"Jpn. J. Allergol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/cm.970280303","article-title":"Control of flagellar bending: A new agenda based on dynein diversity","volume":"28","author":"Brokaw","year":"1994","journal-title":"Cell Motil. Cytoskelet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/cm.970080110","article-title":"Bending patterns of Chlamydomonas flagella: IV. Mutants with defects in inner and outer dynein arms indicate differences in dynein arm function","volume":"8","author":"Brokaw","year":"1987","journal-title":"Cell Motil. Cytoskelet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1159\/000338505","article-title":"Procaterol-stimulated increases in ciliary bend amplitude and ciliary beat frequency in mouse bronchioles","volume":"29","author":"Daikoku","year":"2012","journal-title":"Cell Physiol. Biochem."},{"key":"ref_13","first-page":"S86","article-title":"Activation of ciliary beating by carbocistein via modulation of [Cl\u2212]i and pHi in bronchiolar ciliary cells in mice","volume":"66","author":"Ikeuchi","year":"2016","journal-title":"J. Physiol. Sci."},{"key":"ref_14","first-page":"S137","article-title":"Carbocistein-activated bronchiolar ciliary beating via Cl\u2212- and pH-mediated pathways in mice","volume":"67","author":"Ikeuchi","year":"2017","journal-title":"J. Physiol. Sci."},{"key":"ref_15","first-page":"S86","article-title":"Ciliary beat frequency modulated by PDE1A activity in procaterol stimulated mouse bronchiole","volume":"66","author":"Kogiso","year":"2016","journal-title":"J. Physiol. Sci."},{"key":"ref_16","first-page":"S176","article-title":"Ca2+-regulation of cAMP-activated ciliary beating mediated via PDE1 in mouse bronchiolar cilia","volume":"67","author":"Kogiso","year":"2017","journal-title":"J. Physiol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1007\/s00424-017-1988-9","article-title":"A low [Ca2+]i-induced enhancement of cAMP-activated ciliary beating by PDE1A inhibition in mouse airway cilia","volume":"469","author":"Kogiso","year":"2017","journal-title":"Pfl\u00fcgers Arch. Eur. J. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kogiso, H., Hosogi, S., Ikeuchi, Y., Tanaka, S., Inui, T., Marunaka, Y., and Nakahari, T. (2018). [Ca2+]i modulation of cAMP-stimulated ciliary beat frequency via PDE1 in airway ciliary cells of mice. Exp. Physiol.","DOI":"10.1113\/EP086681"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1126\/science.2500708","article-title":"Activation of salivary secretion: Coupling of cell volume and [Ca2+]i in single cells","volume":"244","author":"Foskett","year":"1989","journal-title":"Science"},{"key":"ref_20","first-page":"385","article-title":"Effect of Hochu-ekki-to (Buzhongyiqitang) on ciliary motility of airway epithelial cells as assessed by the microphoto oscillation technique","volume":"17","author":"Chiyotani","year":"1995","journal-title":"J. Jpn. Soc. Respir. Endoscopy"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1007\/s00424-012-1164-1","article-title":"Methods to measure and analyze ciliary beat activity: Ca2+ influx-mediated cilia mechanosensitivity","volume":"464","author":"Li","year":"2012","journal-title":"Pfl\u00fcgers Arch. Eur. J. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1113\/jphysiol.2003.056481","article-title":"\u03b22-adrenergic regulation of ciliary beat frequency in rat bronchiolar epithelium: Potentiation by isosmotic cell shrinkage","volume":"554","author":"Min","year":"2004","journal-title":"J. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1002\/jssc.201400711","article-title":"Application of isoabsorption plots generated by high-performance liquid chromatography with diode array detection to the development of multicomponent quantitative analysis of traditional herbal medicines","volume":"37","author":"Fang","year":"2014","journal-title":"J. Sep. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jchromb.2017.01.023","article-title":"Simultaneous determination of multiple bioactive components of Bu-zhong-yi-qi-tang in rat tissue by LC-MS\/MS: Application to a tissue distribution study","volume":"1044\u20131045","author":"He","year":"2017","journal-title":"J. Chromotogr. B"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"C49","DOI":"10.1007\/BF01972717","article-title":"Anti-inflammatory properties and inhibition of leukotriene C4 biosynthesis in vitro by flavonoid baicalein from Scutellaria baicalensis GIORGI roots","volume":"39","author":"Butenko","year":"1993","journal-title":"Agents Act."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13256-015-0538-3","article-title":"Aspiration pneumonia and bronchopneumonia in progressive supranuclear palsy treated with quing fei tang: Two case reports","volume":"9","author":"Nozaki","year":"2015","journal-title":"J. Med. Case Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.ijporl.2015.02.002","article-title":"Characteristics of traditional Chinese medicine use for children with allergic rhinitis: A nationwide population-based study","volume":"79","author":"Yen","year":"2015","journal-title":"Int. J. Pediat. Otorhinolaryngol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s12576-018-0591-y","article-title":"Measurement of [Cl\u2212]i unaffected by the cell volume change using MQAE-based two-photon microscopy in airway ciliary cells of mice","volume":"68","author":"Ikeuchi","year":"2018","journal-title":"J. Physiol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1165\/rcmb.2005-0417OC","article-title":"Ciliary beat frequency is maintained at maximal rate in the small airways of mouse lung slices","volume":"35","author":"Delmotte","year":"2006","journal-title":"Am. J. Respir. Cell Mol. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/3\/658\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:56:30Z","timestamp":1760194590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/3\/658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,26]]},"references-count":29,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,3]]}},"alternative-id":["ijms19030658"],"URL":"https:\/\/doi.org\/10.3390\/ijms19030658","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,26]]}}}