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dc.contributor.authorZheng, Kaizhi
dc.contributor.authorLu, Ping
dc.contributor.authorDelpapa, Ellen
dc.contributor.authorBellve, Karl D.
dc.contributor.authorDeng, Ruitang
dc.contributor.authorCondon, Jennifer C.
dc.contributor.authorFogarty, Kevin E.
dc.contributor.authorLifshitz, Lawrence M.
dc.contributor.authorMoore Simas, Tiffany A.
dc.contributor.authorShi, Fangxiong
dc.contributor.authorZhuGe, Ronghua
dc.date2022-08-11T08:10:06.000
dc.date.accessioned2022-08-23T16:55:43Z
dc.date.available2022-08-23T16:55:43Z
dc.date.issued2017-09-01
dc.date.submitted2017-06-13
dc.identifier.citationFASEB J. 2017 Sep;31(9):4037-4052. doi: 10.1096/fj.201601323RR. Epub 2017 May 30. <a href="https://doi.org/10.1096/fj.201601323RR">Link to article on publisher's site</a>
dc.identifier.issn0892-6638 (Linking)
dc.identifier.doi10.1096/fj.201601323RR
dc.identifier.pmid28559440
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42770
dc.description.abstractPreterm birth (PTB) is the leading cause of neonatal mortality and morbidity, with few prevention and treatment options. 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 (i.e., G-protein gustducin and phospholipase C beta2). 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 Ca2+ concentration ([Ca2+]i) and cell shortening induced by uterotonics, and this reversal effect is inhibited by pertussis toxin and by genetic deletion of alpha-gustducin. In human myometrial cells, knockdown of TAS2R14 but not TAS2R10 inhibits ChQ's reversal effect on an oxytocin-induced rise in [Ca2+]i 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 alpha-gustducin knockout 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=28559440&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttps://doi.org/10.1096/fj.201601323RR
dc.subjectCellular and Molecular Physiology
dc.subjectFemale Urogenital Diseases and Pregnancy Complications
dc.subjectMaternal and Child Health
dc.subjectObstetrics and Gynecology
dc.subjectReproductive and Urinary Physiology
dc.subjectWomen's Health
dc.titleBitter taste receptors as targets for tocolytics in preterm labor therapy
dc.typeJournal Article
dc.source.journaltitleFASEB journal : official publication of the Federation of American Societies for Experimental Biology
dc.source.volume31
dc.source.issue9
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/obgyn_pp/125
dc.identifier.contextkey10292813
html.description.abstract<p>Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity, with few prevention and treatment options. 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 (i.e., G-protein gustducin and phospholipase C beta2). 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 Ca2+ concentration ([Ca2+]i) and cell shortening induced by uterotonics, and this reversal effect is inhibited by pertussis toxin and by genetic deletion of alpha-gustducin. In human myometrial cells, knockdown of TAS2R14 but not TAS2R10 inhibits ChQ's reversal effect on an oxytocin-induced rise in [Ca2+]i 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 alpha-gustducin knockout 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.</p>
dc.identifier.submissionpathobgyn_pp/125
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentDepartment of Microbiology and Physiological Systems
dc.contributor.departmentDepartment of Obstetrics and Gynecology
dc.source.pages4037-4052


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