8,273 results match your criteria inhibits channel


Ca-activated Cl channel TMEM16A inhibition by cholesterol promotes angiogenesis in endothelial cells.

J Adv Res 2021 Mar 15;29:23-32. Epub 2020 Sep 15.

Department of Ion Channel Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, China.

Introduction: Ca-activated Cl channel TMEM16A is expressed in endothelial cells, and contributes to many diseases such as hypertension, blood-brain barrier dysfunction, and pulmonary hypertension. It remains unclear whether TMEM16A regulates endothelial angiogenesis, which participates in many physiological and pathological processes. Cholesterol regulates many ion channels including TMEM16A, and high cholesterol levels contribute to endothelial dysfunction. Read More

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GYY4137 and Sodium Hydrogen Sulfide Relaxations Are Inhibited by L-Cysteine and K7 Channel Blockers in Rat Small Mesenteric Arteries.

Front Pharmacol 2021 26;12:613989. Epub 2021 Mar 26.

Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Aarhus University, Aarhus, Denmark.

Donors of HS may be beneficial in treating cardiovascular diseases where the plasma levels of HS are decreased. Therefore, we investigated the mechanisms involved in relaxation of small arteries induced by GYY4137 [(4-methoxyphenyl)-morpholin-4-yl-sulfanylidene-sulfido-λ5-phosphane;morpholin-4-ium], which is considered a slow-releasing HS donor. Sulfides were measured by use of 5,5'-dithiobis-(2-nitro benzoic acid), and small rat mesenteric arteries with internal diameters of 200-250 µm were mounted in microvascular myographs for isometric tension recordings. Read More

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Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca Signaling Pathway.

Front Pharmacol 2021 22;12:606245. Epub 2021 Mar 22.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

XueShuanTong (XST) comprising therapeutically active ginsenosides, a lyophilized extract of roots, is extensively used in traditional Chinese medicine to treat ischemic heart and cerebrovascular diseases. Our recent study shows that treatment with XST inhibits shear-induced thrombosis formation but the underlying mechanism remained unclear. This study aimed to investigate the hypothesis that XST inhibited shear-induced platelet aggregation via targeting the mechanosensitive Ca-permeable Piezo1 channel by performing platelet aggregation assay, Ca imaging and Western blotting analysis. Read More

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Narrative review of the influence of diabetes mellitus and hyperglycemia on colorectal cancer risk and oncological outcomes.

Transl Oncol 2021 Apr 7;14(7):101089. Epub 2021 Apr 7.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tzyou 1st Road, Kaohsiung City 807, Kaohsiung, Taiwan; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Liquid Biopsy and Cohort Research, Taiwan. Electronic address:

Diabetes mellitus (DM) and hyperglycemia have been shown to have significant effects on the incidence, chemoresistance, and prognosis of colorectal cancer (CRC), as well as the outcomes of localized and metastatic CRC. Inflammation and endocrine effects may act as central mechanisms of DM and cancer and stimulate the insulin-like growth factor 1-phosphoinositide 3-kinase-Akt-mammalian target of rapamycin (IGF-1-PI3K-AKT-mTOR) pathway. Dysregulation of the AMP-activated protein kinase (AMPK) pathway leads to metabolic imbalance and indicates cancer risk. Read More

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Icariin ameliorates partial sciatic nerve ligation induced neuropathic pain in rats: an evidence of in silico and in vivo studies.

J Pharm Pharmacol 2021 Apr 3. Epub 2021 Apr 3.

Division of Pharmacology, Institute of Pharmaceutical Technology, Sri Padmavathi Mahila Visvavidyalayam, Tirupati, Andhra Pradesh, India.

Objectives: Neuropathic pain (NP) is a chronic inflammation of the sciatic nerve, associated with complex pathophysiological events like neuronal ectopic discharge with changes in neurotransmitters, growth factors, receptors/ion channels including N-methyl-d-aspartate receptors, Transient receptor cation channels, Voltage-gated calcium channels. All these events eventually lead to inflammation and apoptosis of the sciatic nerve in NP. Icariin (ICA), a natural flavonoid is well known for its anti-inflammatory potential. Read More

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Effects of the Calcium Channel Blocker Otilonium Bromide on Seizure Activity in Rats With Pentylenetetrazole-Induced Convulsions.

Neurochem Res 2021 Apr 3. Epub 2021 Apr 3.

Faculty of Medicine, Department of Physiology, Demiroğlu Bilim University, Istanbul, Turkey.

Millions of people suffer from drug-resistant epilepsy. New therapeutic approaches for removing this life-affecting disease are required. The activation of T-type calcium channels (TTCC) is one of the epileptogenesis mechanisms that cause epilepsy. Read More

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Regulation of Neutrophil Functions by Hv1/VSOP Voltage-Gated Proton Channels.

Int J Mol Sci 2021 Mar 5;22(5). Epub 2021 Mar 5.

Integrative Physiology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita 5650871, Osaka, Japan.

The voltage-gated proton channel, Hv1, also termed VSOP, was discovered in 2006. It has long been suggested that proton transport through voltage-gated proton channels regulate reactive oxygen species (ROS) production in phagocytes by counteracting the charge imbalance caused by the activation of NADPH oxidase. Discovery of Hv1/VSOP not only confirmed this process in phagocytes, but also led to the elucidation of novel functions in phagocytes. Read More

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The Interaction of the Flavonoid Fisetin with Human Glutathione Transferase A1-1.

Metabolites 2021 Mar 23;11(3). Epub 2021 Mar 23.

Laboratory of Enzyme Technology, Department of Biotechnology, School of Food, Biotechnology and Development, Agricultural University of Athens, 75 Iera Odos Street, GR-11855 Athens, Greece.

Glutathione transferases (GSTs) are a family of Phase II detoxification enzymes that are involved in the development of the multidrug resistance (MDR) mechanism in cancer cells and therefore affect the clinical outcome of cancer chemotherapy. The discovery of nontoxic natural compounds as inhibitors for GSTs is a promising approach for chemosensitizing and reversing MDR. Fisetin (7,3',4'-flavon-3-ol) is a plant flavonol present in many plants and fruits. Read More

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Transient receptor potential vanilloid 2 mediates the inhibitory effect of far-infrared irradiation on adipogenic differentiation of tonsil-derived mesenchymal stem cells.

Stem Cell Res 2021 Mar 17;53:102291. Epub 2021 Mar 17.

Department of Molecular Medicine, College of Medicine, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul 07804, Republic of Korea; Graduate Program in System Health Science and Engineering, Ewha Womans University, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul 07804, Republic of Korea. Electronic address:

Aims: Far-infrared (FIR) irradiation inhibits adipogenic differentiation of tonsil-derived mesenchymal stem cells (TMSCs) by activating Ca-dependent protein phosphatase 2B (PP2B), but it stimulates osteogenic differentiation in a PP2B-independent pathway. We investigated the potential involvement of transient receptor potential vanilloid (TRPV) channels, a well-known Ca-permeable channel, in the effects of FIR irradiation on adipogenic or osteogenic differentiation of TMSCs.

Methods: TMSCs, in the absence or presence of activators or inhibitors, were exposed to FIR irradiation followed by adipogenic or osteogenic differentiation, which was assessed using Oil red O or Alizarin red S staining, respectively. Read More

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The gut microbiota metabolite capsiate promotes Gpx4 expression by activating to inhibit intestinal ischemia reperfusion-induced ferroptosis.

Gut Microbes 2021 Jan-Dec;13(1):1-21

Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Ferroptosis, a new type of cell death has been found to aggravate intestinal ischemia/reperfusion (I/R) injury. However, little is known about the changes of gut microbiota and metabolites in intestinal I/R and the role of gut microbiota metabolites on ferroptosis-induced intestinal I/R injury. This study aimed to establish a mouse intestinal I/R model and ileum organoid hypoxia/reoxygenation (H/R) model to explore the changes of the gut microbiota and metabolites during intestinal I/R and protective ability of capsiate (CAT) against ferroptosis-dependent intestinal I/R injury. Read More

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Autophagy contributes to angiotensin II induced dysfunction of HUVECs.

Clin Exp Hypertens 2021 Mar 29:1-12. Epub 2021 Mar 29.

Department of Physiology and Neuroscience, Soochow University - Dushu Lake Campus, Suzhou, China.

: Signal transduction of Angiotensin II (Ang II) induced autophagy and its role in Ang II-induced dysfunction of HUVECs are still unclear.: HUVECs are stimulated with different doses of Ang II (10-9-10-5 mol/L) for different time (6-48 hours). Autophagy-related protein markers: LC3, Beclin-1 and SQSTM1/p62 are measured by western blot. Read More

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The DNA transporter ComEC has metal-dependent nuclease activity that is important for natural transformation.

Mol Microbiol 2021 Mar 26. Epub 2021 Mar 26.

Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, United Kingdom.

In the process of natural transformation bacteria import extracellular DNA molecules for integration into their genome. One strand of the incoming DNA molecule is degraded while the remaining strand is transported across the cytoplasmic membrane. The DNA transport channel is provided by the protein ComEC. Read More

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Essentials in saline pharmacology for nasal or respiratory hygiene in times of COVID-19.

Eur J Clin Pharmacol 2021 Mar 27. Epub 2021 Mar 27.

Department of Biomedical Sciences, Institute of Tropical Medicine and University of Antwerp, Antwerp, Belgium.

Purpose: Nasal irrigation or nebulizing aerosol of isotonic or hypertonic saline is a traditional method for respiratory or nasal care. A recent small study in outpatients with COVID-19 without acute respiratory distress syndrome suggests substantial symptom resolution. We therefore analyzed pharmacological/pharmacodynamic effects of isotonic or hypertonic saline, relevant to SARS-CoV-2 infection and respiratory care. Read More

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Elevation of propofol sensitivity of cardiac I channel by KCNE1 polymorphism D85N.

Br J Pharmacol 2021 Mar 25. Epub 2021 Mar 25.

Department of Physiology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.

Background And Purpose: The slowly activating delayed rectifier K channel (I ), composed of pore-forming KCNQ1 α-subunits and ancillary KCNE1 β-subunits, regulates ventricular repolarization in human heart. Propofol at clinically used concentrations modestly inhibits the intact (wild-type) I channels and is therefore unlikely to appreciably prolong QT interval in electrocardiogram during anesthesia. However, little information is available concerning the inhibitory effect of propofol on I channel associated with its gene variants implicated in QT prolongation. Read More

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ADP-Ribosylation Regulates the Signaling Function of IFN-γ.

Front Immunol 2021 8;12:642545. Epub 2021 Mar 8.

Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Murine T cells express the GPI-anchored ADP-ribosyltransferase 2.2 (ARTC2.2) on the cell surface. Read More

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Simvastatin inhibits oral squamous cell carcinoma by targeting TMEM16A Ca-activated chloride channel.

J Cancer Res Clin Oncol 2021 Mar 23. Epub 2021 Mar 23.

Liaoning Provincial Key Laboratory of Oral Diseases, Department of Oromaxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, 117 Nanjing Bei Jie, Heping District, Shenyang,, 110002, Liaoning, China.

Purpose: Ca-activated chloride channel TMEM16A has been found to be overexpressed in many cancers including head and neck squamous cell carcinoma (HNSCC). Nevertheless, the role of TMEM16A in oral squamous cell carcinoma (OSCC) remains unclear. Although simvastatin is known to produce anti-tumor effect, the mechanisms by which simvastatin inhibits cancer remain unclear. Read More

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Angiotensin II-Vasopressin Interactions in The Regulation of Cardiovascular Functions. Evidence for an Impaired Hormonal Sympathetic Reflex in Hypertension and Congestive Heart Failure.

Endocr Metab Immune Disord Drug Targets 2021 Mar 19. Epub 2021 Mar 19.

Interdisciplinary Department of Medicine-Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases. University of Bari "Aldo Moro", School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124, Bari. Italy.

Introduction: Angiotensin II (ANG II) and vasopressin (VP) interact in several physiological mechanisms, playing a role in arterial hypertension and congestive heart failure. Aim and methods of search: To overview on the primary mechanism involved in the regulation of cardiovascular function, PubMed/Medline was searched, and authors selected original articles and reviews written in English.

Results: Angiotensin II (ANG II) and vasopressin (VP) are involved in several physiological mechanisms. Read More

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Human adenylate kinase 6 regulates WNK1 (with no lysine kinase-1) phosphorylation states and affects ion homeostasis in NT2 cells.

Exp Cell Res 2021 May 18;402(1):112565. Epub 2021 Mar 18.

Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China. Electronic address:

Adenylate kinase 6 (AK6), a nucleus localized phosphotransferase in mammalians, shows ubiquitously expression and broad substrate activity in different tissues and cell types. Although the function of AK6 has been extensively studied in different cancer cell lines, its role in mammalian germline is still unknown. Here we showed that knockdown of AK6 inhibits cell proliferation and promotes cell apoptosis in human testicular carcinoma (NT2 cells). Read More

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Riluzole inhibits Kv4.2 channels acting on the closed and closed inactivated states.

Eur J Pharmacol 2021 Mar 17;899:174026. Epub 2021 Mar 17.

Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio 965 Col, Villas San Sebastián, Colima, COL, 28045, Mexico. Electronic address:

Riluzole is an anticonvulsant drug also used to treat the amyotrophic lateral sclerosis and major depressive disorder. This compound has antiglutamatergic activity and is an important multichannel blocker. However, little is known about its actions on the Kv4. Read More

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A benzopyran with anti-arrhythmic activity is an inhibitor of Kir3.1-containing potassium channels.

J Biol Chem 2021 Mar 10:100535. Epub 2021 Mar 10.

Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts, 02115, USA; Chemistry and Chemical Biology, College of Science, Northeastern University, Boston, MA 02115, USA; Center for Drug Discovery, Northeastern University, Boston, MA 02115, USA. Electronic address:

Atrial fibrillation (AF) is the most commonly diagnosed cardiac arrhythmia and is associated with increased morbidity and mortality. Currently approved AF antiarrhythmic drugs have limited efficacy and/or carry the risk of ventricular pro-arrhythmia. The cardiac acetylcholine activated inwardly rectifying K current (I), composed of Kir3. Read More

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[Anti-inflammatory effects of amantadine and memantine in SARS-CoV-2 infection].

Authors:
Tadeusz Plusa

Pol Merkur Lekarski 2021 Feb;49(289):67-70

Medical Faculty of Lazarski University in Warsaw.

Amantadine and memantine, apart from their action on cholinergic receptors and dopamine secretion, have a significant influence on the inflammatory process, including the so-called "cytokine storm" and reduction of apoptosis and oxidative stress. Amantadine also inhibits the induction of inflammatory factors such as RANTES, activates kinase p38 of mitogen-activated protein (MAP) and c-Jun-NH2-terminal kinases (JNK), which inhibit viral replication. It also significantly inhibits the entry of SARS-CoV-2 into the bronchial epithelial cell and blocks the viroporin proton channel of the virus. Read More

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February 2021

Bupivacaine inhibits a small conductance calcium-activated potassium type 2 channel in human embryonic kidney 293 cells.

BMC Pharmacol Toxicol 2021 Mar 12;22(1):15. Epub 2021 Mar 12.

Department of Pain Management, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 324 Jingwu Road, 250021, Jinan, China.

Background: Bupivacaine blocks many ion channels in the heart muscle, causing severe cardiotoxicity. Small-conductance calcium-activated potassium type 2 channels (SK2 channels) are widely distributed in the heart cells and are involved in relevant physiological functions. However, whether bupivacaine can inhibit SK2 channels is still unclear. Read More

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Mecamylamine inhibits seizure-like activity in CA1-CA3 hippocampus through antagonism to nicotinic receptors.

PLoS One 2021 12;16(3):e0240074. Epub 2021 Mar 12.

Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine.

Cholinergic modulation of hippocampal network function is implicated in multiple behavioral and cognitive states. Activation of nicotinic and muscarinic acetylcholine receptors affects neuronal excitability, synaptic transmission and rhythmic oscillations in the hippocampus. In this work, we studied the ability of the cholinergic system to sustain hippocampal epileptiform activity independently from glutamate and GABA transmission. Read More

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Mechanism of Inhibition of Cytochrome c Oxidase by Triton X-100.

Biochemistry (Mosc) 2021 Jan;86(1):44-58

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia.

It is known that Triton X-100 (TX) reversibly inhibits activity of cytochrome c oxidase (CcO). The mechanism of inhibition is analyzed in this work. The action of TX is not directed to the reaction of CcO with cytochrome c, does not cause transition of the enzyme to the "slow" form, and is not associated with monomerization of the enzyme complex. Read More

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January 2021

Effect of etomidate on the reuniens neuronal activity.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Jan;46(1):39-46

Department of Anesthesiology, First Affiliated Hospitalof Wannan Medical College, Wuhu Anhui 241000, China.

Objectives: To explore the effect of etomidate on the neuronal activity of ventral thalamic reuniens nucleus and the underlying mechanisms.

Methods: Whole-cell patch clamp method was used to explore the effect of etomidate on the activity of ventral thalamic reuniens neurons in the acute brain slices obtained from 4-5 weeks old C57BL/6J mice. The electrophysiological characteristics of ventral thalamic reuniens neurons were recorded in the current clamp mode, and then the effects of etomidate (0. Read More

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January 2021

8--(--methoxycinnamoyl)harpagide Inhibits Influenza A Virus Infection by Suppressing Intracellular Calcium.

Molecules 2021 Feb 15;26(4). Epub 2021 Feb 15.

Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Korea.

Calcium (Ca) dependent signaling circuit plays a critical role in influenza A virus (IAV) infection. The 8--(--methoxycinnamoyl)harpagide (MCH) exhibits pharmacological activities that exert neuroprotective, hepatoprotective, anti-inflammatory and other biological effects. However, not have reports of antiviral effects. Read More

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February 2021

Conflicting Nongenomic Effects of Progesterone in the Myometrium of Pregnant Rats.

Int J Mol Sci 2021 Feb 22;22(4). Epub 2021 Feb 22.

Department of Obstetrics and Gynecology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1010, Japan.

Recently, it has been suggested that progesterone affects the contractile activity of pregnant myometrium via nongenomic pathways; therefore, we aimed to clarify whether progesterone causes and/or inhibits pregnant myometrial contractions via nongenomic pathways. Our in vitro experiments using myometrial strips obtained from rats at 20 days of gestation revealed that progesterone caused myometrial contractions in a concentration- and time-dependent manner at concentrations up to 5 × 10 M; however, this effect decreased at concentrations higher than 5 × 10 M. Similarly, progesterone enhanced oxytocin-induced contractions up to 5 × 10 M and inhibited contractions at concentrations higher than 5 × 10 M. Read More

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February 2021

Deconstruction - Reconstruction: Analysis of the Crucial Structural Elements of GluN2B-Selective, Negative Allosteric NMDA Receptor Modulators with 3-Benzazepine Scaffold.

Cell Physiol Biochem 2021 Mar;55(S3):1-13

GRK 2515, Chemical biology of ion channels (Chembion), Westfälische Wilhelms-Universität Münster, Münster, Germany,

Background/aims: The NMDA receptor plays a key role in the pathogenesis of neurodegenerative disorders including Alzheimer's and Huntington's disease, as well as depression and drug or alcohol dependence. Due to its participation in these pathologies, the development of selective modulators for this ion channel is a promising strategy for rational drug therapy. The prototypical negative allosteric modulator ifenprodil inhibits selectively GluN2B subunit containing NMDA receptors. Read More

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Linalool inhibits the angiogenic activity of endothelial cells by downregulating intracellular ATP levels and activating TRPM8.

Angiogenesis 2021 Mar 2. Epub 2021 Mar 2.

Institute for Clinical & Experimental Surgery, Saarland University, 66421, Homburg, Saarland, Germany.

Angiogenesis crucially contributes to various diseases, such as cancer and diabetic retinopathy. Hence, anti-angiogenic therapy is considered as a powerful strategy against these diseases. Previous studies reported that the acyclic monoterpene linalool exhibits anticancer, anti-inflammatory and anti-oxidative activity. Read More

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