21,004 results match your criteria channel inhibitor

A novel mechanism of Imeglimin-mediated insulin secretion via the cADPR - TRP channel pathway.

J Diabetes Investig 2021 Sep 15. Epub 2021 Sep 15.

Department of Physiology, Division of Integrative Physiology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 3290498, Japan.

Aims/introduction: Imeglimin is a novel oral hypoglycemic agent that improves blood glucose levels through multiple mechanisms of action including enhancement of glucose-stimulated insulin secretion (GSIS), however the details of this mechanism has not been clarified. In the process of GSIS, activation of the transient receptor potential melastatin 2 (TRPM2) channel, a type of non-selective cation channels (NSCCs) in β-cells, promotes plasma membrane depolarization. In the present study, we aimed to examine whether Imeglimin potentiates GSIS via the TRPM2 channel in β-cells. Read More

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September 2021

SMARCA4/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca flux to mitochondria.

Nat Commun 2021 Sep 13;12(1):5404. Epub 2021 Sep 13.

Department of Biochemistry, McGill University, Montreal, QC, Canada.

Inactivating mutations in SMARCA4 and concurrent epigenetic silencing of SMARCA2 characterize subsets of ovarian and lung cancers. Concomitant loss of these key subunits of SWI/SNF chromatin remodeling complexes in both cancers is associated with chemotherapy resistance and poor prognosis. Here, we discover that SMARCA4/2 loss inhibits chemotherapy-induced apoptosis through disrupting intracellular organelle calcium ion (Ca) release in these cancers. Read More

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September 2021

Cadmium induces triglyceride levels via microsomal triglyceride transfer protein (MTTP) accumulation caused by lysosomal deacidification regulated by endoplasmic reticulum (ER) Ca homeostasis.

Chem Biol Interact 2021 Sep 10:109649. Epub 2021 Sep 10.

School of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu, 212013, China; School of Food and Biological Engineering, Zhenjiang, Jiangsu, 212013, China. Electronic address:

Cadmium (Cd) exposure induced lipid metabolic disorder with changes in lipid composition, as well as triglyceride (TG) levels. Liver is the main organ maintaining body TG level and previous studies suggested that Cd exposure might increase TG synthesis but reduce TG uptake in liver. However, the effects of Cd exposure on TG secretion from liver and underlying mechanism are still unclear. Read More

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September 2021

Novel amiloride derivatives that inhibit bacterial motility across multiple strains and stator types.

J Bacteriol 2021 Sep 13:JB0036721. Epub 2021 Sep 13.

School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.

The bacterial flagellar motor (BFM) is a protein complex that confers motility to cells and contributes to survival and virulence. The BFM consists of stators that are ion-selective membrane protein complexes and a rotor that directly connects to a large filament, acting as a propeller. The stator complexes couple ion transit across the membrane to torque that drives rotation of the motor. Read More

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September 2021

Soticlestat, a novel cholesterol 24-hydroxylase inhibitor, reduces seizures and premature death in Dravet syndrome mice.

Epilepsia 2021 Sep 12. Epub 2021 Sep 12.

Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Objective: Dravet syndrome is a severe developmental and epileptic encephalopathy (DEE) most often caused by de novo pathogenic variants in SCN1A. Individuals with Dravet syndrome rarely achieve seizure control and have significantly elevated risk for sudden unexplained death in epilepsy (SUDEP). Heterozygous deletion of Scn1a in mice (Scn1a ) recapitulates several core phenotypes, including temperature-dependent and spontaneous seizures, SUDEP, and behavioral abnormalities. Read More

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September 2021

Involvement of interstitial cells of Cajal in nicotinic acetylcholine receptor-induced relaxation of the porcine lower esophageal sphincter.

Eur J Pharmacol 2021 Sep 9;910:174491. Epub 2021 Sep 9.

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

The interstitial cells of Cajal (ICCs) play an important role in coordinated gastrointestinal motility. The present study aimed to elucidate whether or how ICCs are involved in the lower esophageal sphincter (LES) relaxation induced by stimulation of the nicotinic acetylcholine receptor. The application of 1,1-dimethyl-4-phenyl-piperazinium (DMPP; a nicotinic acetylcholine receptor agonist) induced a transient relaxation in the circular smooth muscle of the porcine LES. Read More

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September 2021


Mol Pharmacol 2021 Sep 9. Epub 2021 Sep 9.

Pharmacology, University of Minnesota, United States

G protein-gated inwardly rectifying K (GIRK/Kir3) channels are critical mediators of excitability in the heart and brain. Enhanced GIRK channel activity has been implicated in the pathogenesis of supraventricular arrhythmias, including atrial fibrillation. The lack of selective pharmacological tools has impeded efforts to investigate the therapeutic potential of cardiac GIRK channel interventions in arrhythmias. Read More

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September 2021

Electrophysiological Effects of the Transient Receptor Potential Melastatin 4 Channel Inhibitor (4-Chloro-2-(2-chlorophenoxy)acetamido) Benzoic Acid (CBA) in Canine Left Ventricular Cardiomyocytes.

Int J Mol Sci 2021 Aug 31;22(17). Epub 2021 Aug 31.

Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.

Transient receptor potential melastatin 4 (TRPM4) plays an important role in many tissues, including pacemaker and conductive tissues of the heart, but much less is known about its electrophysiological role in ventricular myocytes. Our earlier results showed the lack of selectivity of 9-phenanthrol, so CBA ((4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) was chosen as a new, potentially selective inhibitor. Goal: Our aim was to elucidate the effect and selectivity of CBA in canine left ventricular cardiomyocytes and to study the expression of TRPM4 in the canine heart. Read More

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Muscimol Directly Activates the TREK-2 Channel Expressed in GABAergic Neurons through Its N-Terminus.

Int J Mol Sci 2021 Aug 27;22(17). Epub 2021 Aug 27.

Department of Physiology, College of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea.

The two-pore domain K (K) channel, which is involved in setting the resting membrane potential in neurons, is an essential target for receptor agonists. Activation of the γ-aminobutyric acid (GABA) receptors (GABAR and GABAR) reduces cellular excitability through Cl influx and K efflux in neurons. Relatively little is known about the link between GABAR and the K channel. Read More

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Involvement of Reactive Oxygen Species in ABA-Induced Increase in Hydraulic Conductivity and Aquaporin Abundance.

Int J Mol Sci 2021 Aug 24;22(17). Epub 2021 Aug 24.

Ufa Institute of Biology of Ufa Federal Research Centre of the Russian Academy of Sciences, Pr. Octyabrya 69, 450054 Ufa, Russia.

The role of reactive oxygen species (ROS) in ABA-induced increase in hydraulic conductivity was hypothesized to be dependent on an increase in aquaporin water channel (AQP) abundance. Single ABA application or its combination with ROS manipulators (ROS scavenger ascorbic acid and NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI)) were studied on detached roots of barley plants. We measured the osmotically driven flow rate of xylem sap and calculated root hydraulic conductivity. Read More

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Characterization of Compound-Specific, Concentration-Independent Biophysical Properties of Sodium Channel Inhibitor Mechanism of Action Using Automated Patch-Clamp Electrophysiology.

Front Pharmacol 2021 23;12:738460. Epub 2021 Aug 23.

Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary.

We have developed an automated patch-clamp protocol that allows high information content screening of sodium channel inhibitor compounds. We have observed that individual compounds had their specific signature patterns of inhibition, which were manifested irrespective of the concentration. Our aim in this study was to quantify these properties. Read More

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(-)-Carveol Prevents Gastric Ulcers via Cytoprotective, Antioxidant, Antisecretory and Immunoregulatory Mechanisms in Animal Models.

Front Pharmacol 2021 23;12:736829. Epub 2021 Aug 23.

Postgraduate Program in Natural and Synthetic Bioactive Products, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa, Brazil.

(-)-Carveol (-Mentha-6,8-dien-2-ol) is a monocyclic monoterpenic alcohol, present in essential oils of plant species such as , and in spices such as (cumin). Pharmacological studies report its antitumor, antimicrobial, neuroprotective, vasorelaxant, antioxidant and anti-inflammatory activity. The objective of this study was to evaluate the acute non-clinical oral toxicity, gastroprotective activity of monoterpene (-)-Carveol in animal models and the related mechanisms of action. Read More

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Effects of Naringin on Cardiomyocytes From a Rodent Model of Type 2 Diabetes.

Front Pharmacol 2021 23;12:719268. Epub 2021 Aug 23.

Department of Research, Mount Sinai Medical Center, Miami, FL, United States.

Diabetic cardiomyopathy (DCM) is a primary disease in diabetic patients characterized by diastolic dysfunction leading to heart failure and death. Unfortunately, even tight glycemic control has not been effective in its prevention. We have found aberrant diastolic Ca concentrations ([Ca]), decreased glucose transport, elevated production of reactive oxygen species (ROS), and increased calpain activity in cardiomyocytes from a murine model (db/db) of type 2 diabetes (T2D). Read More

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Metal organic framework derived one-dimensional porous Fe/N-doped carbon nanofibers with enhanced catalytic performance.

J Hazard Mater 2021 Aug 24;416:126101. Epub 2021 May 24.

Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science & Technology, Nanjing 210094, PR China. Electronic address:

The aggregation of metal nanoparticles and collapse of precursor metal organic frameworks (MOFs) structure during the carbonization process largely hamper the catalytic performance of MOFs-derived carbon catalysts. Here, we report hollow and porous one-dimensional Fe/N-doped carbon nanofibers (Fe/NCNFs) for activating peroxymonosulfate (PMS), which was obtained by immobilizing Fe-MIL-101 on polyacrylonitrile (PAN) nanofibers via electrospinning technique followed by pyrolysis. The presence of one-dimensional PAN channel suppresses the agglomeration tendency of metal particles during the carbonisation process of Fe-MIL-101, resulting in a uniform dispersion of nanoparticles and an increase of catalytic active sites. Read More

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Acid-sensing ion channel 1 contributes to pulmonary arterial smooth muscle cell depolarization following hypoxic pulmonary hypertension.

J Physiol 2021 Sep 6. Epub 2021 Sep 6.

Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM, 87131-0001, USA.

Key Points: In pulmonary hypertensive patients and animal models of pulmonary hypertension, the resting membrane potential (E ) of pulmonary arterial smooth muscle cells (PASMCs) is persistently depolarized. In addition to the well-established reduction of K  conductance, we show non-selective cation channel (NSCC) currents are increased and essential to the persistent E depolarization in PASMCs following chronic hypoxia (CH)-induced pulmonary hypertension. The current study provides novel evidence that acid-sensing ion channel 1 (ASIC1)-mediated Na influx induces membrane depolarization and regulates E in PASMCs following CH exposure. Read More

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September 2021

The antidepressant Sertraline inhibits CatSper Ca2+ channels in human sperm.

Hum Reprod 2021 Sep 6. Epub 2021 Sep 6.

Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.

Study Question: Do selective serotonin reuptake inhibitor (SSRI) antidepressants affect the function of human sperm?

Summary Answer: The SSRI antidepressant Sertraline (e.g. Zoloft) inhibits the sperm-specific Ca2+ channel CatSper and affects human sperm function in vitro. Read More

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September 2021

The anti-nociceptive activity of naringenin passes through L-arginine/NO/cGMP/KATP channel pathway and opioid receptors.

Behav Pharmacol 2021 Oct;32(7):590-598

Department of Neuroscience, Faculty of Advanced Technologies in Medical Sciences, Iran University of Medical Sciences, Tehran.

As a promising flavonoid, naringenin has shown potential anti-inflammatory and antioxidant properties mainly in inflammatory pain models by oral administration. Therefore, we investigated the antinociceptive activity of this compound by intraperitoneally (i.p. Read More

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October 2021

Amelioration of Scopolamine-induced Learning and Memory Impairment by the TRPV4 Inhibitor HC067047 in ICR Mice.

Neurosci Lett 2021 Sep 1:136209. Epub 2021 Sep 1.

Clinical Anatomy & Reproductive Medicine Application Institute, Hengyang Medical College, University of South China, 421001 Hengyang, Hunan, China; China Key Laboratory Of Brain Science Research & Transformation In Tropical Environment Of Hainan Province, Hainan Medical University, 571199, Haikou, Hai nan China. Electronic address:

Alzheimer's disease (AD) is one of the most common causes of neurodegenerative diseases in the elderly. Cholinergic dysfunction is one of the pathological hallmarks of AD and leads to learning and memory impairment. Transient receptor potential vanilloid 4(TRPV4), a nonselective cation channel, is involved in learning and memory functions. Read More

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September 2021

Neuroprotective effects of the CTK 01512-2 toxin against neurotoxicity induced by 3-nitropropionic acid in rats.

Neurotoxicology 2021 Aug 31;87:30-42. Epub 2021 Aug 31.

Laboratory of Toxicology Research, The Federal University of Health Science of Porto Alegre (UFCSPA), Rio Grande do Sul, Brazil. Electronic address:

The mitochondrial inhibitor 3-nitropropionic acid (3-NP) induces excitotoxicity. The authors hypothesized that CTK 01512-2, a recombinant peptide calcium channel N-type blocker, and the TRPA1 antagonist, could show neuroprotective effects. The male Wistar rats received 3-NP [25 mg/kg (i. Read More

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Astrocyte Pannexin 1 Suppresses LPS-Induced Inflammatory Responses to Protect Neuronal SH-SY5Y Cells.

Front Cell Neurosci 2021 12;15:710820. Epub 2021 Aug 12.

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Reactive astrogliosis is a key hallmark of inflammatory responses in the pathogenesis of brain injury, including Parkinson's disease (PD), but its role and regulatory mechanisms are not fully understood. Pannexin 1 (Panx 1) is a membrane channel that mediates substance release in many neurodegenerative diseases. However, the role of astrocyte Panx 1 in the regulation of PD-like neuroinflammation remains elusive. Read More

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Mechanisms of gefitinib-induced QT prolongation.

Eur J Pharmacol 2021 Aug 30;910:174441. Epub 2021 Aug 30.

Xiamen Cardiovascular Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361004, China. Electronic address:

Gefitinib, a tyrosine kinase inhibitor, was the first targeted therapy for non-small cell lung cancer (NSCLC). Gefitinib could block human Ether-à-go-go-Related Gene (hERG) channel, an important target in drug-induced long QT syndrome. However, it is unclear whether gefitinib could induce QT interval prolongation. Read More

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Structural mechanism of TRPV3 channel inhibition by the plant-derived coumarin osthole.

EMBO Rep 2021 Sep 2:e53233. Epub 2021 Sep 2.

Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.

TRPV3, a representative of the vanilloid subfamily of TRP channels, is predominantly expressed in skin keratinocytes and has been implicated in cutaneous sensation and associated with numerous skin pathologies and cancers. TRPV3 is inhibited by the natural coumarin derivative osthole, an active ingredient of Cnidium monnieri, which has been used in traditional Chinese medicine for the treatment of a variety of human diseases. However, the structural basis of channel inhibition by osthole has remained elusive. Read More

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September 2021

Abnormal levels of mitochondrial proteins in plasma neuronal extracellular vesicles in major depressive disorder.

Mol Psychiatry 2021 Sep 1. Epub 2021 Sep 1.

Department of Obstetrics, Gynecology and Reproductive Sciences, University of California School of Medicine, San Francisco, CA, USA.

To characterize neuronal mitochondrial abnormalities in major depressive disorder (MDD), functional mitochondrial proteins (MPs) extracted from enriched plasma neuron-derived extracellular vesicles (NDEVs) of MDD participants (n = 20) were quantified before and after eight weeks of treatment with a selective serotonin reuptake inhibitor (SSRI). Pretreatment baseline NDEV levels of the transcriptional type 2 nuclear respiratory factor (NRF2) which controls mitochondrial biogenesis and many anti-oxidant gene responses, regulators of diverse neuronal mitochondrial functions cyclophilin D (CYPD) and mitofusin-2 (MFN2), leucine zipper EF-hand containing transmembrane 1 protein (LETM1) component of a calcium channel/calcium channel enhancer, mitochondrial tethering proteins syntaphilin (SNPH) and myosin VI (MY06), inner membrane electron transport complexes I (subunit 6) and III (subunit 10), the penultimate enzyme of nicotinamide adenine dinucleotide (NAD) generation nicotinamide mononucleotide adenylytransferase 2 (NMNAT2), and neuronal mitochondrial metabolic regulatory and protective factors humanin and mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c) all were significantly lower than those of NDEVs from matched controls (n = 10), whereas those of pro-neurodegenerative NADase Sterile Alpha and TIR motif-containing protein 1 (SARM1) were higher. The baseline NDEV levels of transcription factor A mitochondrial (TFAM) and the transcriptional master-regulator of mitochondrial biogenesis PPAR γ coactivator-1α (PGC-1α) showed no differences between MDD participants and controls. Read More

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September 2021

Absence of effect of steady state bempedoic acid on cardiac repolarization: Results of a thorough QT/QTc study in healthy volunteers.

Clin Transl Sci 2021 Aug 31. Epub 2021 Aug 31.

Esperion Therapeutics, Inc., Ann Arbor, Michigan, USA.

Bempedoic acid is an inhibitor of adenosine triphosphate-citrate lyase approved for use in adults with hypercholesterolemia. Nonclinical studies assessed binding to the human ether-a-go-go-related gene (hERG) potassium channel in vitro and the effect of bempedoic acid on QT/QTc in cynomolgus monkeys. A randomized, double-blind, parallel-design clinical study assessed the effects of steady-state bempedoic acid at a supratherapeutic dose (240 mg/day, 33. Read More

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Preconditioning the rat heart with 5-azacytidine attenuates myocardial ischemia/reperfusion injury via PI3K/GSK3β and mitochondrial K signaling axis.

J Biochem Mol Toxicol 2021 Aug 30:e22911. Epub 2021 Aug 30.

School of Chemical and Biotechnology, Vascular Biology Lab, SASTRA Deemed University, Thanjavur, Tamilnadu, India.

5-Azacytidine is well known for its clinical usage in cancer treatments. The present study investigates the role of 5-azacytidine as a cardioprotective agent to ameliorate ischemia/reperfusion (I/R) injury. The cardioprotective effect of 5-azacytidine was evaluated in three experimental models: in vitro, ex vivo, and in vivo. Read More

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Vasospastic angina in a chronic myeloid leukemia patient treated with nilotinib.

Cardiooncology 2021 Aug 27;7(1):31. Epub 2021 Aug 27.

Department of Cardiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

Background: Nilotinib, a second-generation BCR-ABL tyrosine kinase inhibitor (TKI), is highly effective in the treatment of patients with chronic myeloid leukemia (CML), despite being more vasculotoxic than older TKIs such as imatinib. Herein, we present a case of nilotinib-associated vasospastic angina confirmed by an acetylcholine spasm provocation test.

Case Presentation: A 62-year-old CML patient treated with 300 mg nilotinib twice daily complained of several episodes of rest angina and was hospitalized at our institution. Read More

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Periorbital Nociception in a Progressive Multiple Sclerosis Mouse Model Is Dependent on TRPA1 Channel Activation.

Pharmaceuticals (Basel) 2021 Aug 23;14(8). Epub 2021 Aug 23.

Graduated Program in Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria 97105-900, RS, Brazil.

Headaches are frequently described in progressive multiple sclerosis (PMS) patients, but their mechanism remains unknown. Transient receptor potential ankyrin 1 (TRPA1) was involved in neuropathic nociception in a model of PMS induced by experimental autoimmune encephalomyelitis (PMS-EAE), and TRPA1 activation causes periorbital and facial nociception. Thus, our purpose was to observe the development of periorbital mechanical allodynia (PMA) in a PMS-EAE model and evaluate the role of TRPA1 in periorbital nociception. Read More

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Cepharanthine, a novel selective ANO1 inhibitor with potential for lung adenocarcinoma therapy.

Biochim Biophys Acta Mol Cell Res 2021 Aug 25;1868(12):119132. Epub 2021 Aug 25.

Research Center for Differentiation and Development of Traditional Chinese Medicine Basic Theory, Jiangxi University of Traditional Chinese Medicine, Nanchang, China; Key Laboratory for Research on Active Ingredients in Natural Medicine of Jiangxi Province, Yichun University, Yichun, China.. Electronic address:

Anoctamin-1 (ANO1), also known as transmembrane protein 16A (TMEM16A), is identified as a Ca-activated Cl channel that is expressed in many organs and tissues. It is involved in numerous major physiological functions and especially in tumor growth. By screening 530 natural compounds, we identified cepharanthine as a potent blocker of ANO1 channels with an IC of 11. Read More

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Constitutive phosphorylation as a key regulator of TRPM8 channel function.

J Neurosci 2021 Aug 26. Epub 2021 Aug 26.

Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile (USACH), 9160000 Santiago, Chile.

In mammals, environmental cold sensing carried out by peripheral cold thermoreceptor neurons mostly depends on TRPM8, an ion channel that has evolved to become the main molecular cold transducer. This TRP channel is activated by cold, cooling compounds such as menthol, voltage, and rises in osmolality. TRPM8 function is regulated by kinase activity that phosphorylates the channel under resting conditions. Read More

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Molecular Dynamics-Derived Pharmacophore Model Explaining the Nonselective Aspect of K10.1 Pore Blockers.

Int J Mol Sci 2021 Aug 20;22(16). Epub 2021 Aug 20.

Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia.

The K10.1 voltage-gated potassium channel is highly expressed in 70% of tumors, and thus represents a promising target for anticancer drug discovery. However, only a few ligands are known to inhibit K10. Read More

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