دورية أكاديمية
أعرض في EDS

Anoctamin 1 antagonism potentiates conventional tocolytic-mediated relaxation of pregnant human uterine smooth muscle.

التفاصيل البيبلوغرافية
العنوان: Anoctamin 1 antagonism potentiates conventional tocolytic-mediated relaxation of pregnant human uterine smooth muscle.
المؤلفون: Hyuga S; Department of Anesthesiology, Columbia University College of Physicians and Surgeons, 622 W. 168th St. P&S Box 46, New York, NY, 10032, USA., Parry RC; Department of Anesthesiology, Columbia University College of Physicians and Surgeons, 622 W. 168th St. P&S Box 46, New York, NY, 10032, USA., Danielsson J; Department of Anesthesiology, Columbia University College of Physicians and Surgeons, 622 W. 168th St. P&S Box 46, New York, NY, 10032, USA., Vink J; Department of Obstetrics & Gynecology, Columbia University College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA., Fu XW; Department of Anesthesiology, Columbia University College of Physicians and Surgeons, 622 W. 168th St. P&S Box 46, New York, NY, 10032, USA., Wu A; Department of Anesthesiology, Columbia University College of Physicians and Surgeons, 622 W. 168th St. P&S Box 46, New York, NY, 10032, USA., Dan W; Department of Anesthesiology, Columbia University College of Physicians and Surgeons, 622 W. 168th St. P&S Box 46, New York, NY, 10032, USA., Yim PD; Department of Anesthesiology, Columbia University College of Physicians and Surgeons, 622 W. 168th St. P&S Box 46, New York, NY, 10032, USA., Gallos G; Department of Anesthesiology, Columbia University College of Physicians and Surgeons, 622 W. 168th St. P&S Box 46, New York, NY, 10032, USA. gg2125@cumc.columbia.edu.
المصدر: The journal of physiological sciences : JPS [J Physiol Sci] 2021 Feb 22; Vol. 71 (1), pp. 7. Date of Electronic Publication: 2021 Feb 22.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Japan Country of Publication: Japan NLM ID: 101262417 Publication Model: Electronic Cited Medium: Internet ISSN: 1880-6562 (Electronic) Linking ISSN: 18806546 NLM ISO Abbreviation: J Physiol Sci Subsets: MEDLINE
أسماء مطبوعة: Publication: Tokyo : Springer Japan
Original Publication: Tokyo, Japan : Physiological Society of Japan, c2006-
مواضيع طبية MeSH: Anoctamin-1/*antagonists & inhibitors , Muscle Relaxation/*drug effects , Muscle, Smooth/*drug effects , Nifedipine/*pharmacology , Terbutaline/*pharmacology , Uterus/*physiology, Benzbromarone/pharmacology ; Female ; Gene Expression Regulation/drug effects ; Humans ; Pregnancy ; Tissue Culture Techniques ; Tocolytic Agents/pharmacology ; Uricosuric Agents/pharmacology ; ortho-Aminobenzoates/pharmacology
مستخلص: Background: Currently available tocolytic agents are not effective treatment for preterm labor beyond 48 h. A major reason is the development of maternal side effects which preclude the maintenance of an effective steady-state drug concentration. One strategy that can mitigate these side effects is utilizing synergistic drug combinations to reduce the drug concentrations necessary to elicit a clinical effect. We have previously shown that three anoctamin 1 (ANO1) antagonists mediate potent relaxation of precontracted human uterine smooth muscle (USM). In this study, we aimed to determine whether a combination of sub-relaxatory doses of tocolytic drugs in current clinical use [the L-type voltage-gated calcium channel (VGCC) blocker, nifedipine (NIF); and the β 2 -adrenergic (β2AR) agonist, terbutaline (TRB)] will potentiate USM relaxation with two ANO1 antagonists [benzbromarone (BB) and MONNA (MN)].
Objective: This study sought to examine the synergistic potency and mechanistic basis of two ANO1 antagonists with currently available tocolytic drugs. Functional endpoints assessed included relaxation of pre-contracting pregnant human USM tissue, inhibition of intracellular calcium release, and reduction of spontaneous transient inward current (STIC) recordings in human uterine smooth muscle cells.
Methods: Human myometrial strips and primary human USM cells were used in organ bath and calcium flux experiments with different combinations of sub-threshold doses of ANO1 antagonists and terbutaline or nifedipine to determine if ANO1 antagonists potentiate tocolytic drugs.
Results: The combination of sub-threshold doses of two ANO1 antagonists and current tocolytic drugs demonstrate a significant degree of synergy to relax human pregnant USM compared to the effects achieved when these drugs are administered individually.
Conclusion: A combination of sub-threshold doses of VGCC blocker and β2AR agonist with ANO1 antagonists potentiates relaxation of oxytocin-induced contractility and calcium flux in human USM ex vivo. Our findings may serve as a foundation for novel tocolytic drug combinations.
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معلومات مُعتمدة: R01 HL122340 United States HL NHLBI NIH HHS; R01 HD082251 United States HD NICHD NIH HHS; 1R01HD082251 United States NH NIH HHS; K08 HD088758 United States HD NICHD NIH HHS
فهرسة مساهمة: Keywords: ANO1; Calcium-activated chloride channel; TMEM16A; Tocolytics; Uterine smooth muscle
المشرفين على المادة: 0 (Anoctamin-1)
0 (N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid)
0 (Tocolytic Agents)
0 (Uricosuric Agents)
0 (ortho-Aminobenzoates)
4POG0RL69O (Benzbromarone)
I9ZF7L6G2L (Nifedipine)
N8ONU3L3PG (Terbutaline)
تواريخ الأحداث: Date Created: 20210223 Date Completed: 20211110 Latest Revision: 20231215
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9352361
DOI: 10.1186/s12576-021-00792-3
PMID: 33618673
قاعدة البيانات: MEDLINE
الوصف
تدمد:1880-6562
DOI:10.1186/s12576-021-00792-3