Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
: To determine whether acid-sensing ion channel 1 (ASIC1)-sodium-potassium-chloride cotransporter 1 (NKCC1) signaling pathway participates in chronic visceral pain of adult rats with neonatal maternal deprivation (NMD). : Chronic visceral pain was detected by colorectal distension (CRD). Western blotting and Immunofluorescence were performed to detect the expression and location of ASIC1 and NKCC1. Whole-cell patch-clamp recordings were performed to record spinal synaptic transmission. : The excitatory synaptic transmission was enhanced and the inhibitory synaptic transmission was weakened in the spinal dorsal horn of NMD rats. ASIC1 and NKCC1 protein expression in the spinal dorsal horn was significantly up-regulated in NMD rats. Incubation of Amiloride reduced the amplitude of mEPSCs. Incubation of Bumetanide (BMT) increased the amplitude of mIPSCs. Intrathecal injection of ASIC1 or NKCC1 inhibitors reversed the threshold of CRD in NMD rats. Also, Amiloride treatment significantly reversed the expression of NKCC1 in the spinal dorsal horn of NMD rats. : Our data suggest that the ASIC1-NKCC1 signaling pathway is involved in chronic visceral pain in NMD rats.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874109 | PMC |
| http://dx.doi.org/10.3389/fnmol.2020.611179 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
From gut to brain: donepezil and nimodipine combination therapy improves cognitive deficits in Alzheimer's disease via gut microbiota and metabolites.
Biochem Biophys Res Commun
September 2025
Department of Pharmaceutical Analysis, College of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250118, China. Electronic address:
Donepezil (DNP) is often combined with nimodipine (NMD) for the treatment of Alzheimer's disease (AD). However, its underlying mechanisms remain poorly understood. This study integrated pharmacodynamics, microbiomics, and fecal metabolomics analysis to explore the therapeutic potential and mechanism of DNP + NMD in AD.
View Article and Find Full Text PDFClC-1 Inhibition as a Mechanism for Accelerating Skeletal Muscle Recovery After Neuromuscular Block in Rats.
Nat Commun
October 2024
NMD Pharma, Aarhus, Denmark.
Neuromuscular blocking agents are used commonly to induce skeletal muscle relaxation during surgery. While muscle relaxation facilitates surgical procedures and tracheal intubation, adequate recovery of muscle function after surgery is required to support pulmonary function, and even mild residual neuromuscular block increases the risk of severe postoperative pulmonary complications. While recovery of muscle function after surgery involving neuromuscular blocking agents can be monitored and, in addition, be accelerated by use of current antagonists (reversal agents), there is a clear clinical need for a safe drug to antagonize all types of neuromuscular blocking agents.
View Article and Find Full Text PDFAdipocyte endothelin B receptor activation inhibits adiponectin production and causes insulin resistance in obese mice.
Acta Physiol (Oxf)
October 2024
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Aims: Endothelin-1 (ET-1) is elevated in patients with obesity and adipose tissue of obese mice fed high-fat diet (HFD); however, its contribution to the pathophysiology of obesity is not fully understood. Genetic loss of endothelin type B receptors (ET) improves insulin sensitivity in rats and leads to increased circulating adiponectin, suggesting that ET activation on adipocytes may contribute to obesity pathophysiology. We hypothesized that elevated ET-1 in obesity promotes insulin resistance by reducing the secretion of insulin sensitizing adipokines, via ET receptor.
View Article and Find Full Text PDFProinflammatory cytokines suppress nonsense-mediated RNA decay to impair regulated transcript isoform processing in pancreatic β cells.
Front Endocrinol (Lausanne)
April 2024
Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom.
Introduction: Proinflammatory cytokines are implicated in pancreatic ß cell failure in type 1 and type 2 diabetes and are known to stimulate alternative RNA splicing and the expression of nonsense-mediated RNA decay (NMD) components. Here, we investigate whether cytokines regulate NMD activity and identify transcript isoforms targeted in ß cells.
Methods: A luciferase-based NMD reporter transiently expressed in rat INS1(832/13), human-derived EndoC-ßH3, or dispersed human islet cells is used to examine the effect of proinflammatory cytokines (Cyt) on NMD activity.
The ClC-1 chloride channel inhibitor NMD670 improves skeletal muscle function in rat models and patients with myasthenia gravis.
Sci Transl Med
March 2024
NMD Pharma A/S, Palle Juul-Jensens Boulevard 82, 8200 Aarhus N, Denmark.
Myasthenia gravis (MG) is a neuromuscular disease that results in compromised transmission of electrical signals at the neuromuscular junction (NMJ) from motor neurons to skeletal muscle fibers. As a result, patients with MG have reduced skeletal muscle function and present with symptoms of severe muscle weakness and fatigue. ClC-1 is a skeletal muscle specific chloride (Cl) ion channel that plays important roles in regulating neuromuscular transmission and muscle fiber excitability during intense exercise.
View Article and Find Full Text PDF