This article proposes a new approach to the modeling of the molecular-level mechanism of ligand-receptor interaction for Ca2+ receptor binding site. Chemically induced dynamic nuclear polarization (CIDNP) technique has been used to unravel fine details of the reaction in the model system composed of one of the known Ca2+ antagonist drugs, nifedipine (NF), and isolated amino acid residuals (e.g. tyrosine [Tyr]) of Ca2+ receptor binding site. It has been conclusively demonstrated that the reaction between NF and Tyr resulting in the oxidation product--nitroso form of NF--obeys the radical mechanism. CIDNP data in combination with the results of mathematical modeling of the structures of ligand-receptor complexes have allowed to propose the mechanism of the interaction of NF with Ca2+ receptor binding site.
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http://dx.doi.org/10.1562/0031-8655(2004)080<0565:PSOTIO>2.0.CO;2 | DOI Listing |
J Control Release
January 2025
Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Waltham, MA, USA.
Cota is a lipidated dual GLP-1 and Glucagon receptor agonist that was investigated for the treatment of various metabolic diseases, it is designed for once daily subcutaneous administration. Invasive daily injections often result in poor patient compliance with chronic disease, and here, we demonstrate an innovative strategy of encapsulating reversible cota self-assembled fibers within an in-situ forming depot of low molecular weight poly(lactic-co-glycolic) acid (LWPLGA) for sustained delivery GLP-1 and Glucagon receptor agonist with controlled burst release. This could be a suitable alternative to other sustained delivery strategies for fibrillating peptides.
View Article and Find Full Text PDFPLoS Biol
January 2025
Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) CCT UNS-CONICET, Bahía Blanca, Argentina.
The DAF-2/insulin/insulin-like growth factor signaling (IIS) pathway plays an evolutionarily conserved role in regulating reproductive development, life span, and stress resistance. In Caenorhabditis elegans, DAF-2/IIS signaling is modulated by an extensive array of insulin-like peptides (ILPs) with diverse spatial and temporal expression patterns. However, the release dynamics and specific functions of these ILPs in adapting to different environmental conditions remain poorly understood.
View Article and Find Full Text PDFBiochem Soc Trans
January 2025
Departamento de Ciencias Médicas Básicas, Facultad de Ciencias de la Salud-sección Medicina, Universidad de La Laguna, Tenerife, ES-38071, Spain.
Large conductance voltage- and calcium-activated potassium channels (BK channels) are extensively found throughout the central nervous system and play a crucial role in various neuronal functions. These channels are activated by a combination of cell membrane depolarisation and an increase in intracellular calcium concentration, provided by calcium sources located close to BK. In 2001, Isaacson and Murphy first demonstrated the coupling of BK channels with N-methyl-D-aspartate receptors (NMDAR) in olfactory bulb neurons.
View Article and Find Full Text PDFJ Neurochem
January 2025
School of Life Science, Nanchang University, Nanchang, China.
Activation of the brain-penetrant beta3-adrenergic receptor (Adrb3) is implicated in the treatment of depressive disorders. Enhancing GABAergic inputs from interneurons onto pyramidal cells of prefrontal cortex (PFC) represents a strategy for antidepressant therapies. Here, we probed the effects of the activation of Adrb3 on GABAergic transmission onto pyramidal neurons in the PFC using in vitro electrophysiology.
View Article and Find Full Text PDFJ Neurochem
January 2025
Molecular Horizons, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, New South Wales, Australia.
GABA receptor (GABAR) activation is known to alleviate pain by reducing neuronal excitability, primarily through inhibition of high voltage-activated (HVA) calcium (Ca2.2) channels and potentiating G protein-coupled inwardly rectifying potassium (GIRK) channels. Although the analgesic properties of small molecules and peptides have been primarily tested on isolated murine dorsal root ganglion (DRG) neurons, emerging strategies to develop, study, and characterise human pluripotent stem cell (hPSC)-derived sensory neurons present a promising alternative.
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