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A New Slow Releasing, H(2)S Generating Compound, GYY4137 Relaxes Spontaneous and Oxytocin-Stimulated Contractions of Human and Rat Pregnant Myometrium

Better tocolytics are required to help prevent preterm labour. The gaseotransmitter Hydrogen sulphide (H(2)S) has been shown to reduce myometrial contractility and thus is of potential interest. However previous studies used NaHS, which is toxic and releases H(2)S as a non-physiological bolus and th...

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Autores principales: Robinson, Hayley, Wray, Susan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459845/
https://www.ncbi.nlm.nih.gov/pubmed/23029460
http://dx.doi.org/10.1371/journal.pone.0046278
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author Robinson, Hayley
Wray, Susan
author_facet Robinson, Hayley
Wray, Susan
author_sort Robinson, Hayley
collection PubMed
description Better tocolytics are required to help prevent preterm labour. The gaseotransmitter Hydrogen sulphide (H(2)S) has been shown to reduce myometrial contractility and thus is of potential interest. However previous studies used NaHS, which is toxic and releases H(2)S as a non-physiological bolus and thus alternative H(2)S donors are sought. GYY4137 has been developed to slowly release H(2)S and hence better reflect endogenous physiological release. We have examined its effects on spontaneous and oxytocin-stimulated contractility and compared them to NaHS, in human and rat myometrium, throughout gestation. The effects on contractility in response to GYY4137 (1 nM–1 mM) and NaHS (1 mM) were examined on myometrial strips from, biopsies of women undergoing elective caesarean section or hysterectomy, and from non-pregnant, 14, 18, 22 day (term) gestation or labouring rats. In pregnant rat and human myometrium dose-dependent and significant decreases in spontaneous contractions were seen with increasing concentrations of GYY4137, which also reduced underlying Ca transients. GYY4137 and NaHS significantly reduced oxytocin-stimulated and high-K depolarised contractions as well as spontaneous activity. Their inhibitory effects increased as gestation advanced, but were abruptly reversed in labour. Glibenclamide, an inhibitor of ATP-sensitive potassium (K(ATP)) channels, abolished the inhibitory effect of GYY4137. These data suggest (i) H(2)S contributes to uterine quiescence from mid-gestation until labor, (ii) that H(2)S affects L-type calcium channels and K(ATP) channels reducing Ca entry and thereby myometrial contractions, (iii) add to the evidence that H(2)S plays a physiological role in relaxing myometrium, and thus (iv) H(2)S is an attractive target for therapeutic manipulation of human myometrial contractility.
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spelling pubmed-34598452012-10-01 A New Slow Releasing, H(2)S Generating Compound, GYY4137 Relaxes Spontaneous and Oxytocin-Stimulated Contractions of Human and Rat Pregnant Myometrium Robinson, Hayley Wray, Susan PLoS One Research Article Better tocolytics are required to help prevent preterm labour. The gaseotransmitter Hydrogen sulphide (H(2)S) has been shown to reduce myometrial contractility and thus is of potential interest. However previous studies used NaHS, which is toxic and releases H(2)S as a non-physiological bolus and thus alternative H(2)S donors are sought. GYY4137 has been developed to slowly release H(2)S and hence better reflect endogenous physiological release. We have examined its effects on spontaneous and oxytocin-stimulated contractility and compared them to NaHS, in human and rat myometrium, throughout gestation. The effects on contractility in response to GYY4137 (1 nM–1 mM) and NaHS (1 mM) were examined on myometrial strips from, biopsies of women undergoing elective caesarean section or hysterectomy, and from non-pregnant, 14, 18, 22 day (term) gestation or labouring rats. In pregnant rat and human myometrium dose-dependent and significant decreases in spontaneous contractions were seen with increasing concentrations of GYY4137, which also reduced underlying Ca transients. GYY4137 and NaHS significantly reduced oxytocin-stimulated and high-K depolarised contractions as well as spontaneous activity. Their inhibitory effects increased as gestation advanced, but were abruptly reversed in labour. Glibenclamide, an inhibitor of ATP-sensitive potassium (K(ATP)) channels, abolished the inhibitory effect of GYY4137. These data suggest (i) H(2)S contributes to uterine quiescence from mid-gestation until labor, (ii) that H(2)S affects L-type calcium channels and K(ATP) channels reducing Ca entry and thereby myometrial contractions, (iii) add to the evidence that H(2)S plays a physiological role in relaxing myometrium, and thus (iv) H(2)S is an attractive target for therapeutic manipulation of human myometrial contractility. Public Library of Science 2012-09-27 /pmc/articles/PMC3459845/ /pubmed/23029460 http://dx.doi.org/10.1371/journal.pone.0046278 Text en © 2012 Robinson, Wray http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Robinson, Hayley
Wray, Susan
A New Slow Releasing, H(2)S Generating Compound, GYY4137 Relaxes Spontaneous and Oxytocin-Stimulated Contractions of Human and Rat Pregnant Myometrium
title A New Slow Releasing, H(2)S Generating Compound, GYY4137 Relaxes Spontaneous and Oxytocin-Stimulated Contractions of Human and Rat Pregnant Myometrium
title_full A New Slow Releasing, H(2)S Generating Compound, GYY4137 Relaxes Spontaneous and Oxytocin-Stimulated Contractions of Human and Rat Pregnant Myometrium
title_fullStr A New Slow Releasing, H(2)S Generating Compound, GYY4137 Relaxes Spontaneous and Oxytocin-Stimulated Contractions of Human and Rat Pregnant Myometrium
title_full_unstemmed A New Slow Releasing, H(2)S Generating Compound, GYY4137 Relaxes Spontaneous and Oxytocin-Stimulated Contractions of Human and Rat Pregnant Myometrium
title_short A New Slow Releasing, H(2)S Generating Compound, GYY4137 Relaxes Spontaneous and Oxytocin-Stimulated Contractions of Human and Rat Pregnant Myometrium
title_sort new slow releasing, h(2)s generating compound, gyy4137 relaxes spontaneous and oxytocin-stimulated contractions of human and rat pregnant myometrium
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459845/
https://www.ncbi.nlm.nih.gov/pubmed/23029460
http://dx.doi.org/10.1371/journal.pone.0046278
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