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

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Shunsuke Hyuga ◽  
Robert C. Parry ◽  
Jennifer Danielsson ◽  
Joy Vink ◽  
Xiao Wen Fu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Side Effects ◽  
Calcium Release ◽  
Drug Combinations ◽  
Calcium Flux ◽  
Organ Bath ◽  
Anoctamin 1 ◽  
Uterine Smooth Muscle ◽  
Drug Concentrations ◽  
Threshold Doses

Abstract 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 β2-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.

scholarly journals Calcium-activated chloride channels anoctamin 1 and 2 promote murine uterine smooth muscle contractility

2014 ◽  
Vol 211 (6) ◽  
pp. 688.e1-688.e10 ◽  
Author(s):  
Kyra Bernstein ◽  
Joy Y. Vink ◽  
Xiao Wen Fu ◽  
Hiromi Wakita ◽  
Jennifer Danielsson ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Chloride Channels ◽  
Anoctamin 1 ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Uterine Smooth Muscle

Presence of the Ca2+-activated chloride channel anoctamin 1 in the urethra and its role in excitatory neurotransmission

2012 ◽  
Vol 302 (3) ◽  
pp. F390-F400 ◽  
Author(s):  
Maria Sancho ◽  
Angeles García-Pascual ◽  
Domingo Triguero
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Chloride Channel ◽  
Calcium Release ◽  
Calcium Influx ◽  
Muscle Cells ◽  
Anoctamin 1 ◽  
Urethral Smooth Muscle ◽  
Excitatory Responses ◽  
A Minor

We investigated the cellular distribution of the calcium-activated chloride channel (CaCC), anoctamin 1, in the urethra of mice, rats, and sheep by both immunofluorescence and PCR. We studied its role in urethral contractility by examining the effects of chloride-free medium and of several CaCC inhibitors on noradrenergic and cholinergic excitatory responses, and on nitrergic relaxations in urethral preparations. In all species analyzed, CaCC played a key role in urethral contractions, influencing smooth muscle cells activated by increases in intracellular calcium, probably due to calcium influx but with a minor contribution by IP3-mediated calcium release. The participation of CaCC in relaxant responses was negligible. Strong anoctamin 1 immunoreactivity was detected in the smooth muscle cells and urothelia of sheep, rat, and mouse urethra, but not in the interstitial cells of Cajal (ICC) in any of these species. RT-PCR confirmed the expression of anoctamin 1 mRNA in the rat urethra. This anoctamin 1 in urethral smooth muscle probably mediates the activity of chloride in contractile responses in different species, However, the lack of anoctamin 1 in ICCs challenges its proposed role in regulating urethral contractility in a manner similar to that observed in the gut.

scholarly journals Dietary Selenium Influences Calcium Release and Activation of MLCK in Uterine Smooth Muscle of Rats

2013 ◽  
Vol 154 (1) ◽  
pp. 127-133 ◽  
Author(s):  
Mengyao Guo ◽  
Tingting Lv ◽  
Fangning Liu ◽  
Haiyang Yan ◽  
Teng Wei ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Calcium Release ◽  
Dietary Selenium ◽  
Uterine Smooth Muscle

scholarly journals Functional comparison of anoctamin 1 antagonists on human uterine smooth muscle contractility and excitability

2018 ◽  
Vol 54 (0) ◽  
pp. 28-42 ◽  
Author(s):  
Shunsuke Hyuga ◽  
Jennifer Danielsson ◽  
Joy Vink ◽  
Xiao Wen Fu ◽  
Ronald Wapner ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Anoctamin 1 ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Uterine Smooth Muscle

scholarly journals Mechanism of Spasmogenic Activity Stimulated by Aqueous Ethanolic Leaf Extract of Mucuna pruriens on Isolated Uterine Muscle of Albino Rats

2019 ◽  
pp. 1-10
Author(s):  
B. Francis ◽  
C. N. Uchendu ◽  
R. I. Obidike
Keyword(s):  
Smooth Muscle ◽  
Leaf Extract ◽  
Mucuna Pruriens ◽  
Albino Rats ◽  
Organ Bath ◽  
Atropine Sulphate ◽  
Uterine Smooth Muscle ◽  
Uterine Muscle ◽  
Dose Dependent ◽  
Ethanolic Leaf Extract

Aims: To investigate the effect of aqueous ethanolic leaf extract of this medicinal plant on isolated uterine smooth muscle strips of the rat and to determine its mechanism of action. Study Design:  Laboratory-experimental design was used in this study. Place and Duration of Study: The study was carried out in the Department of Veterinary Physiology and Biochemistry of Michael Okpara University of Agriculture, Umudike, Nigeria, Department of Pharmacology and Toxicology of the Faculty of Pharmacy, University of Nigeria, Nsukka, and the Department of Veterinary Physiology and Pharmacology, University of Nigeria, Nsukka, Nigeria between June and October 2014. Methodology: Fresh leaves of Mucuna pruriens were identified and collected by a taxonomist from Nsukka, Nigeria. The leaves were then air dried and pulverized into powder. This was then subjected to cold extraction using petroleum ether (70-90) and 70% aqueous ethanol, after which the extract was left to dry at room temperature. Estrogenised uterine strips (12mm) were harvested from non-pregnant, sexually matured albino rats (180 g -250 g) and suspended in a 35ml organ bath containing Krebs’ physiological salt solution. The organ bath was connected to an isometric electronic force displacement transducer and a physiograph. Drugs such as Salbutamol, Isoprenaline, Adrenaline, Propranolol, Atipamezole and Prazosin were used as either agonists or antagonists to determine the mechanism of action of the extract. Atropine sulphate and Cyproheptadine were also used as test drugs. Concentrations of these drugs presented in the body of this work represent the final nutrient bath concentrations. Results: M. pruriens caused a dose -dependent increase in uterine muscle contraction with an EC50 of 0.88 mg/ml, n=4. The contraction was unaffected by atropine sulphate (0.042 µmol), but abolished by salbutamol (0.012-0.4 µmol), isoprenaline (0.06-0.23 µmol), and adrenaline (16 nmol). The uterine muscle contractions were enhanced by propranolol (1 µmol) in a dose- dependent manner. Prazosin (0.069-0.14 µmol) and atipamezole (3.3-13.7 nmol) were unable to abolish contractions stimulated by the extract. However, 0.2 µmol of cyproheptadine caused 80% suppression of the extract –induced uterine contraction Conclusion: It is concluded that aqueous ethanolic leaf extract of M. pruriens, has ability to cause uterine smooth muscle contraction hence, justifies its reported use traditionally as a uterine stimulant. This contraction is most likely exerted via the 5-HT receptor activation (activated by low concentrations of serotonin).

Anti-Diarrheal Drug Repositioning in Tumour Cell Cytotoxicity

2019 ◽  
Vol 19 (8) ◽  
pp. 1037-1047 ◽  
Author(s):  
Jihene Elloumi-Mseddi ◽  
Dhouha Msalbi ◽  
Raouia Fakhfakh ◽  
Sami Aifa
Keyword(s):  
Side Effects ◽  
Anticancer Drugs ◽  
Tumour Cell ◽  
Caspase 3 ◽  
Drug Repositioning ◽  
Brdu Incorporation ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Ic50 Values ◽  
Mcf 7

Background:Drug repositioning is becoming an ideal strategy to select new anticancer drugs. In particular, drugs treating the side effects of chemotherapy are the best candidates.Objective:In this present work, we undertook the evaluation of anti-tumour activity of two anti-diarrheal drugs (nifuroxazide and rifaximin).Methods:Anti-proliferative effect against breast cancer cells (MDA-MB-231, MCF-7 and T47D) was assessed by MTT analysis, the Brdu incorporation, mitochondrial permeability and caspase-3 activity.Results:Both the drugs displayed cytotoxic effects on MCF-7, T47D and MDA-MB-231 cells. The lowest IC50 values were obtained on MCF-7 cells after 24, 48 and 72 hours of treatment while T47D and MDA-MB-231 were more resistant. The IC50 values on T47D and MDA-MB-231 cells became significantly low after 72 hours of treatment showing a late cytotoxicity effect especially of nifuroxazide but still less important than that of MCF-7 cells. According to the IC50 values, the non-tumour cell line HEK293 seems to be less sensitive to cytotoxicity especially against rifaximin. Both the drugs have shown an accumulation of rhodamine 123 as a function of the rise of their concentrations while the Brdu incorporation decreased. Despite the absence of a significant difference in the cell cycle between the treated and non-treated MCF-7 cells, the caspase-3 activity increased with the drug concentrations rise suggesting an apoptotic effect.Conclusion:Nifuroxazide and rifaximin are used to overcome the diarrheal side effect of anticancer drugs. However, they have shown to be anti-tumour drugs which make them potential dual effective drugs against cancer and the side effects of chemotherapy.

Leiomyoma with Bizarre Nuclei (Symplastic Leiomyoma) in the Paratubal Cyst Wall: Report of a Rare Case

2021 ◽  
pp. 106689692199779
Author(s):  
Murat Celik
Keyword(s):  
Differential Diagnosis ◽  
Smooth Muscle ◽  
Cyst Wall ◽  
Rare Case ◽  
Clinical Behavior ◽  
Uterine Smooth Muscle ◽  
Smooth Muscle Neoplasm ◽  
Histological Variants ◽  
Eosinophilic Cytoplasm ◽  
Paratubal Cyst

Leiomyoma is a benign mesenchymal tumor that develops from smooth muscle cells. It can present in various histological variants. Leiomyoma with bizarre nuclei is an infrequent variant of uterine smooth muscle neoplasm. It is characterized by focally or diffusely distributed bizarre cells on the background of a typical leiomyoma. These bizarre cells are large, multinucleated, or multilobulated and have an eosinophilic cytoplasm. Even though leiomyomas with bizarre nuclei display benign clinical behavior, their differential diagnosis from leiomyosarcoma can sometimes be difficult. Leiomyoma has been described most commonly in the uterus. There is no case of leiomyoma originating from paratubal cysts described in the literature. In this article, we present a rare case of leiomyoma with bizarre nuclei originating from a paratubal cyst.

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