Butylidenephthalide facilitates contractions via nonspecific binding to receptors in isolated guinea-pig vas deferens

Context: Butylidenephthalide (Bdph) has been reported to inhibit rat uterine contractions, but significantly potentiate the noradrenaline (NA)-induced contractions in guinea-pig vas deferens (GPVDs). Objective: The present study elucidates the binding specificity of Bdph in GPVD to potentiate contra...

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Autores principales:	Chung-Hung Shih, Chi-Ming Chen, Wun-Chang Ko
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	ca2+ channel blockers clonidine noradrenaline postjunctional k+ channel blockade voltage-dependent ca2+ channels Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/a8adf0e772d2433eae8cbc64f156518e
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spelling	oai:doaj.org-article:a8adf0e772d2433eae8cbc64f156518e2021-11-17T14:21:56ZButylidenephthalide facilitates contractions via nonspecific binding to receptors in isolated guinea-pig vas deferens1388-02091744-511610.1080/13880209.2019.1619781https://doaj.org/article/a8adf0e772d2433eae8cbc64f156518e2019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1619781https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: Butylidenephthalide (Bdph) has been reported to inhibit rat uterine contractions, but significantly potentiate the noradrenaline (NA)-induced contractions in guinea-pig vas deferens (GPVDs). Objective: The present study elucidates the binding specificity of Bdph in GPVD to potentiate contractions. Materials and methods: Electrical field stimulation (EFS, supramaximal voltage, 1 ms and 1 Hz) or exogenous NA (50 μM) was applied to the GPVD in Krebs or 1/10 Mg-Tyrode’s solution, respectively. After the clonidine (10 nM)-induced twitch inhibition or the exogenous NA-induced contractions reached a constant, Bdph (50 µM) was added 2 min prior to the subsequent addition of NA (50 µM). Three experiments were performed. In the presence of Bdph (100 μM), the release of NA in the medium and remaining NA content in the tissues were determined after EFS-stimulation. Results: Bdph (100 μM) significantly antagonized the clonidine (10 nM)-induced twitch inhibition from 22.5 ± 2.1 to –11.4 ± 1.6% (n = 6) and dibutyryl-cAMP (300 μM) from 25.7 ± 3.2 to 7.9 ± 4.0% (n = 8). Bdph (100 μM) significantly increased the electrically stimulated release of NA from 393.0 ± 109.5 to 1000.0 ± 219.1 ng/g (n = 6). Bdph (50 μM) potentiated the exogenous NA (50 μM)-induced contractions from 3.0 ± 0.06 to 3.9 ± 0.06 g (n = 3), but after washout of Bdph, the response to NA gradually curtailed. Discussion and conclusions: Bdph action may be through the nonspecific binding of the butylidene group to prejunctional α2- and postjunctional α1-adrenoceptors to reversibly block K+ channels, and irreversibly block VDCCs on the smooth muscle cell membrane, respectively.Chung-Hung ShihChi-Ming ChenWun-Chang KoTaylor & Francis Grouparticleca2+ channel blockersclonidinenoradrenalinepostjunctional k+ channel blockadevoltage-dependent ca2+ channelsTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 380-384 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	ca2+ channel blockers clonidine noradrenaline postjunctional k+ channel blockade voltage-dependent ca2+ channels Therapeutics. Pharmacology RM1-950
spellingShingle	ca2+ channel blockers clonidine noradrenaline postjunctional k+ channel blockade voltage-dependent ca2+ channels Therapeutics. Pharmacology RM1-950 Chung-Hung Shih Chi-Ming Chen Wun-Chang Ko Butylidenephthalide facilitates contractions via nonspecific binding to receptors in isolated guinea-pig vas deferens
description	Context: Butylidenephthalide (Bdph) has been reported to inhibit rat uterine contractions, but significantly potentiate the noradrenaline (NA)-induced contractions in guinea-pig vas deferens (GPVDs). Objective: The present study elucidates the binding specificity of Bdph in GPVD to potentiate contractions. Materials and methods: Electrical field stimulation (EFS, supramaximal voltage, 1 ms and 1 Hz) or exogenous NA (50 μM) was applied to the GPVD in Krebs or 1/10 Mg-Tyrode’s solution, respectively. After the clonidine (10 nM)-induced twitch inhibition or the exogenous NA-induced contractions reached a constant, Bdph (50 µM) was added 2 min prior to the subsequent addition of NA (50 µM). Three experiments were performed. In the presence of Bdph (100 μM), the release of NA in the medium and remaining NA content in the tissues were determined after EFS-stimulation. Results: Bdph (100 μM) significantly antagonized the clonidine (10 nM)-induced twitch inhibition from 22.5 ± 2.1 to –11.4 ± 1.6% (n = 6) and dibutyryl-cAMP (300 μM) from 25.7 ± 3.2 to 7.9 ± 4.0% (n = 8). Bdph (100 μM) significantly increased the electrically stimulated release of NA from 393.0 ± 109.5 to 1000.0 ± 219.1 ng/g (n = 6). Bdph (50 μM) potentiated the exogenous NA (50 μM)-induced contractions from 3.0 ± 0.06 to 3.9 ± 0.06 g (n = 3), but after washout of Bdph, the response to NA gradually curtailed. Discussion and conclusions: Bdph action may be through the nonspecific binding of the butylidene group to prejunctional α2- and postjunctional α1-adrenoceptors to reversibly block K+ channels, and irreversibly block VDCCs on the smooth muscle cell membrane, respectively.
format	article
author	Chung-Hung Shih Chi-Ming Chen Wun-Chang Ko
author_facet	Chung-Hung Shih Chi-Ming Chen Wun-Chang Ko
author_sort	Chung-Hung Shih
title	Butylidenephthalide facilitates contractions via nonspecific binding to receptors in isolated guinea-pig vas deferens
title_short	Butylidenephthalide facilitates contractions via nonspecific binding to receptors in isolated guinea-pig vas deferens
title_full	Butylidenephthalide facilitates contractions via nonspecific binding to receptors in isolated guinea-pig vas deferens
title_fullStr	Butylidenephthalide facilitates contractions via nonspecific binding to receptors in isolated guinea-pig vas deferens
title_full_unstemmed	Butylidenephthalide facilitates contractions via nonspecific binding to receptors in isolated guinea-pig vas deferens
title_sort	butylidenephthalide facilitates contractions via nonspecific binding to receptors in isolated guinea-pig vas deferens
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/a8adf0e772d2433eae8cbc64f156518e
work_keys_str_mv	AT chunghungshih butylidenephthalidefacilitatescontractionsvianonspecificbindingtoreceptorsinisolatedguineapigvasdeferens AT chimingchen butylidenephthalidefacilitatescontractionsvianonspecificbindingtoreceptorsinisolatedguineapigvasdeferens AT wunchangko butylidenephthalidefacilitatescontractionsvianonspecificbindingtoreceptorsinisolatedguineapigvasdeferens
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Butylidenephthalide facilitates contractions via nonspecific binding to receptors in isolated guinea-pig vas deferens

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