Over the past few decades a combination of electrophysiological, morphological and molecular approaches has enabled the different populations of vagal and spinal afferents that innervate the bowel to be characterized. The sensitivity of these afferents is determined by their location in the gut wall, their relationship with other cells and structures and the receptors and ion channels that they express on their nerve terminals. An important feature of this innervation is that it is upregulated during injury, inflammation and ischaemia through changes in receptors and ion channels that determine excitability and sensitivity. In recent studies we have sought to identify how sensory mechanisms are influenced as part of the normal ageing process. Attenuated signaling was evident in different gastrointestinal afferent subpopulations conveying low and high threshold mechanosensory information and there was impairment in the ability of sensory neurons to sensitize in response to chemical mediators such as 5-HT. These sensory deficits may contribute to altered bowel habits with age and the prevalence of incontinence in the elderly.
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http://dx.doi.org/10.1007/978-3-319-27592-5_8 | DOI Listing |
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India.
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Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, Romania.
Cenobamate is a new and highly effective antiseizure compound used for the treatment of adults with focal onset seizures and particularly for epilepsy resistant to other antiepileptic drugs. It acts on multiple targets, as it is a positive allosteric activator of γ-aminobutyric acid type A (GABA) receptors and an inhibitor of neuronal sodium channels, particularly of the late or persistent Na current. We recently evidenced the inhibitory effects of cenobamate on the peak and late current component of the human cardiac isoform hNav1.
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December 2024
Centre for Research University Services (CeSAR), Università degli Studi di Cagliari, S.S. 554 Bivio per Sestu, 09042 Monserrato, Italy.
2,8-Dithia-5-aza-2,6-pyridinophane () has been used as a receptor unit in the construction of the conjugated redox chemosensor 5-ferrocenylmethyl-2,8-dithia-5-aza-2,6-pyridinophane (). In order to further explore the coordination chemistry of , and comparatively, that of its structural analogue 2,11-dithia-5,8-diaza-2,6-pyridinophane (), featuring two secondary nitrogen atoms in the macrocyclic unit, the crystal structures of the new synthesised complexes [Pb()(ClO)]·½CHCN, [Cu()](ClO)·CHCN and [Cd()(NO)]NO were determined by X-ray diffraction analysis. The electrochemical response of towards the metal ions Cu, Zn, Cd, Hg, and Pb was investigated by cyclic voltammetry (CV) in CHCl/CHCN 0.
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December 2024
Structural Bioinformatics Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Tykistökatu 6, 20520 Turku, Finland.
Transient receptor potential vanilloid (TRPV) 4 is involved in signaling pathways specifically mediating pain and inflammation, making it a promising target for the treatment of various painful and inflammatory conditions. However, only one drug candidate targeting TRPV4 has entered the clinical trials. To identify potential TRPV4 inhibitors for drug development, we screened a library of ion channel-modulating compounds using both structure- and ligand-based virtual screening approaches.
View Article and Find Full Text PDFCommun Biol
January 2025
Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea.
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