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[PMID]: | 28559440 |
[Au] Autor: | Zheng K; Lu P; Delpapa E; Bellve K; Deng R; Condon JC; Fogarty K; Lifshitz LM; Simas TAM; Shi F; ZhuGe R |
[Ad] Endereço: | College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China. |
[Ti] Título: | Bitter taste receptors as targets for tocolytics in preterm labor therapy. |
[So] Source: | FASEB J;31(9):4037-4052, 2017 Sep. | [Is] ISSN: | 1530-6860 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | 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 ( G-protein gustducin and phospholipase C ß2). 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 concentration ([Ca ] ) and cell shortening induced by uterotonics, and this reversal effect is inhibited by pertussis toxin and by genetic deletion of α-gustducin. In human myometrial cells, knockdown of TAS2R14 but not TAS2R10 inhibits ChQ's reversal effect on an oxytocin-induced rise in [Ca ] 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 α-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.-Zheng, 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. |
[Mh] Termos MeSH primário: |
Regulação da Expressão Gênica/fisiologia Miométrio/citologia Trabalho de Parto Prematuro/tratamento farmacológico Receptores Acoplados a Proteínas-G/metabolismo
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[Mh] Termos MeSH secundário: |
Albuterol Animais Cálcio/metabolismo Cloroquina Feminino Seres Humanos Sulfato de Magnésio Camundongos Contração Muscular/efeitos dos fármacos Contração Muscular/fisiologia Músculo Liso/efeitos dos fármacos Músculo Liso/fisiologia Ocitocina/farmacologia Fenantrolinas Gravidez Compostos de Amônio Quaternário Receptores Acoplados a Proteínas-G/genética Transducina/genética Transducina/metabolismo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Phenanthrolines); 0 (Quaternary Ammonium Compounds); 0 (Receptors, G-Protein-Coupled); 147979-21-3 (gustducin); 4YK5Z54AT2 (denatonium benzoate); 50-56-6 (Oxytocin); 7487-88-9 (Magnesium Sulfate); 886U3H6UFF (Chloroquine); EC 3.6.5.1 (Transducin); QF8SVZ843E (Albuterol); SY7Q814VUP (Calcium); W4X6ZO7939 (1,10-phenanthroline) |
[Em] Mês de entrada: | 1710 |
[Cu] Atualização por classe: | 171109 |
[Lr] Data última revisão:
| 171109 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170601 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1096/fj.201601323RR |
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