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Uterine contraction is a central feature of PTB, so gaining new insights into the mechanisms of this contraction and consequently identifying novel targets for tocolytics are essential for more successful management of PTB. Here we report that myometrial cells from human and mouse express bitter taste receptors (TAS2Rs) and their canonical signaling components (\n                    <jats:italic>i.e.<\/jats:italic>\n                    , G\u2010protein gustducin and phospholipase C \u03b22). Bitter tastants can completely relax myometrium precontracted by different uterotonics. In isolated single mouse myometrial cells, a phenotypical bitter tastant (chloroquine, ChQ) reverses the rise in intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    concentration ([Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    ) and cell shortening induced by uterotonics, and this reversal effect is inhibited by pertussis toxin and by genetic deletion of a\u2010gustducin. In human myometrial cells, knockdown of TAS2R14 but not TAS2R10 inhibits ChQ\u2019s reversal effect on an oxytocin\u2010induced rise in [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    . Finally, ChQ prevents mouse PTBs induced by bacterial endotoxin LPS or progesterone receptor antagonist mifepristone more often than current commonly used tocolytics, and this prevention is largely lost in \u03b1\u2010gustducin\u2010knockout mice. Collectively, our results reveal that activation of the canonical TAS2R signaling system in myometrial cells produces profound relaxation of myometrium precontracted by a broad spectrum of contractile agonists, and that targeting TAS2Rs is an attractive approach to developing effective tocolytics for PTB management.\u2014Zheng, K., Lu, P., Delpapa, E., Bellve, K., Deng, R., Condon, J. C., Fogarty, K., Lifshitz, L. M., Simas, T. A. M., Shi, F., ZhuGe, R. Bitter taste receptors as targets for tocolytics in preterm labor therapy. FASEB J. 31, 4037\u20134052 (2017).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                    \u2014Branco, Renato Chaves Souto, Camargo, Rafael Ludemann, Batista, Thiago Martins, Vettorazzi, Jean Franciesco, Borck, Patricia Cristine, dos Santos\u2010Silva, Junia Carolina Rebelo, Boschero, Antonio Carlos, Zoppi, Claudio Cesar, Carneiro, Everardo Magalh\u00e4es Bitter taste receptors as targets for tocolytics in preterm labor therapy. FASEB J. 31, 4037\u20134052 (2017)\n                  <\/jats:p>","DOI":"10.1096\/fj.201601323rr","type":"journal-article","created":{"date-parts":[[2017,5,30]],"date-time":"2017-05-30T20:55:30Z","timestamp":1496177730000},"page":"4037-4052","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Bitter taste receptors as targets for tocolytics in preterm labor therapy"],"prefix":"10.1096","volume":"31","author":[{"given":"Kaizhi","family":"Zheng","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"},{"name":"Department of Microbiology and Physiological Systems University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Physiological Systems University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Delpapa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Bellve","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruitang","family":"Deng","sequence":"additional","affiliation":[{"name":"College of Pharmacy University of Rhode Island  Kingstown Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer C.","family":"Condon","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology School of Medicine Wayne State University  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Fogarty","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence M.","family":"Lifshitz","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany A. Moore","family":"Simas","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Massachusetts Medical School  Worcester Massachusetts USA"},{"name":"Department of Pediatrics University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangxiong","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronghua","family":"ZhuGe","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Physiological Systems University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4755-10-S1-S2"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1353\/pbm.2014.0036","article-title":"The perfect storm: preterm birth, neurodevelopmental mechanisms, and autism causation","volume":"57","author":"Erdei C.","year":"2014","journal-title":"Perspect. 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