دورية أكاديمية
Anoctamin 1 antagonism potentiates conventional tocolytic-mediated relaxation of pregnant human uterine smooth muscle.
العنوان: | Anoctamin 1 antagonism potentiates conventional tocolytic-mediated relaxation of pregnant human uterine smooth muscle. |
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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 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 |
تدمد: | 1880-6562 |
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DOI: | 10.1186/s12576-021-00792-3 |