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...

Descripción completa

Detalles Bibliográficos
Autores principales: Yart, Lucile, Frieden, Maud, Konig, Stéphane, Cohen, Marie, Martinez de Tejada, Begoña
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