Cargando…
Dual effect of nifedipine on pregnant human myometrium contractility: Implication of TRPC1
Nifedipine, an L‐type voltage‐gated Ca(2+) channel (L‐VGCC) blocker, is one of the most used tocolytics to treat preterm labor. In clinical practice, nifedipine efficiently decreases uterine contractions, but its efficacy is limited over time, and repeated or maintained nifedipine‐based tocolysis ap...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306527/ https://www.ncbi.nlm.nih.gov/pubmed/34988986 http://dx.doi.org/10.1002/jcp.30666 |
_version_ | 1784752558270578688 |
---|---|
author | Yart, Lucile Frieden, Maud Konig, Stéphane Cohen, Marie Martinez de Tejada, Begoña |
author_facet | Yart, Lucile Frieden, Maud Konig, Stéphane Cohen, Marie Martinez de Tejada, Begoña |
author_sort | Yart, Lucile |
collection | PubMed |
description | Nifedipine, an L‐type voltage‐gated Ca(2+) channel (L‐VGCC) blocker, is one of the most used tocolytics to treat preterm labor. In clinical practice, nifedipine efficiently decreases uterine contractions, but its efficacy is limited over time, and repeated or maintained nifedipine‐based tocolysis appears to be ineffective in preventing preterm birth. We aimed to understand why nifedipine has short‐lasting efficiency for the inhibition of uterine contractions. We used ex vivo term pregnant human myometrial strips treated with cumulative doses of nifedipine. We observed that nifedipine inhibited spontaneous myometrial contractions in tissues with high and regular spontaneous contractions. By contrast, nifedipine appeared to increase contractions in tissues with low and/or irregular spontaneous contractions. To investigate the molecular mechanisms activated by nifedipine in myometrial cells, we used the pregnant human myometrial cell line PHM1‐41 that does not express L‐VGCC. The in vitro measurement of intracellular Ca(2+) showed that high doses of nifedipine induced an important intracellular Ca(2+) entry in myometrial cells. The inhibition or downregulation of the genes encoding for store‐operated Ca(2+) entry channels from the Orai and transient receptor potential‐canonical (TRPC) families in PHM1‐41 cells highlighted the implication of TRPC1 in nifedipine‐induced Ca(2+) entry. In addition, the use of 2‐APB in combination with nifedipine on human myometrial strips tends to confirm that the pro‐contractile effect induced by nifedipine on myometrial tissues may involve the activation of TRPC channels. |
format | Online Article Text |
id | pubmed-9306527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93065272022-07-28 Dual effect of nifedipine on pregnant human myometrium contractility: Implication of TRPC1 Yart, Lucile Frieden, Maud Konig, Stéphane Cohen, Marie Martinez de Tejada, Begoña J Cell Physiol Research Articles Nifedipine, an L‐type voltage‐gated Ca(2+) channel (L‐VGCC) blocker, is one of the most used tocolytics to treat preterm labor. In clinical practice, nifedipine efficiently decreases uterine contractions, but its efficacy is limited over time, and repeated or maintained nifedipine‐based tocolysis appears to be ineffective in preventing preterm birth. We aimed to understand why nifedipine has short‐lasting efficiency for the inhibition of uterine contractions. We used ex vivo term pregnant human myometrial strips treated with cumulative doses of nifedipine. We observed that nifedipine inhibited spontaneous myometrial contractions in tissues with high and regular spontaneous contractions. By contrast, nifedipine appeared to increase contractions in tissues with low and/or irregular spontaneous contractions. To investigate the molecular mechanisms activated by nifedipine in myometrial cells, we used the pregnant human myometrial cell line PHM1‐41 that does not express L‐VGCC. The in vitro measurement of intracellular Ca(2+) showed that high doses of nifedipine induced an important intracellular Ca(2+) entry in myometrial cells. The inhibition or downregulation of the genes encoding for store‐operated Ca(2+) entry channels from the Orai and transient receptor potential‐canonical (TRPC) families in PHM1‐41 cells highlighted the implication of TRPC1 in nifedipine‐induced Ca(2+) entry. In addition, the use of 2‐APB in combination with nifedipine on human myometrial strips tends to confirm that the pro‐contractile effect induced by nifedipine on myometrial tissues may involve the activation of TRPC channels. John Wiley and Sons Inc. 2022-01-05 2022-03 /pmc/articles/PMC9306527/ /pubmed/34988986 http://dx.doi.org/10.1002/jcp.30666 Text en © 2021 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Yart, Lucile Frieden, Maud Konig, Stéphane Cohen, Marie Martinez de Tejada, Begoña Dual effect of nifedipine on pregnant human myometrium contractility: Implication of TRPC1 |
title | Dual effect of nifedipine on pregnant human myometrium contractility: Implication of TRPC1 |
title_full | Dual effect of nifedipine on pregnant human myometrium contractility: Implication of TRPC1 |
title_fullStr | Dual effect of nifedipine on pregnant human myometrium contractility: Implication of TRPC1 |
title_full_unstemmed | Dual effect of nifedipine on pregnant human myometrium contractility: Implication of TRPC1 |
title_short | Dual effect of nifedipine on pregnant human myometrium contractility: Implication of TRPC1 |
title_sort | dual effect of nifedipine on pregnant human myometrium contractility: implication of trpc1 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306527/ https://www.ncbi.nlm.nih.gov/pubmed/34988986 http://dx.doi.org/10.1002/jcp.30666 |
work_keys_str_mv | AT yartlucile dualeffectofnifedipineonpregnanthumanmyometriumcontractilityimplicationoftrpc1 AT friedenmaud dualeffectofnifedipineonpregnanthumanmyometriumcontractilityimplicationoftrpc1 AT konigstephane dualeffectofnifedipineonpregnanthumanmyometriumcontractilityimplicationoftrpc1 AT cohenmarie dualeffectofnifedipineonpregnanthumanmyometriumcontractilityimplicationoftrpc1 AT martinezdetejadabegona dualeffectofnifedipineonpregnanthumanmyometriumcontractilityimplicationoftrpc1 |