The nicotinic acetylcholine receptor (nAChR) from fish electric organs and vertebrate neuromuscular junctions is a well-characterized transmembrane allosteric protein, composed of four polypeptide chains assembled into a heterologous pentamer alpha2betagammadelta, which carries ACh-binding sites and contains cation-selective channel-forming elements. Topographical mapping of residues contributing to the ligand-binding domain (LBD) of Torpedo nAChR was achieved with different site-directed antagonist or agonist probes. Over two decades of biochemical investigation led to the identification of three discontinuous domains on alpha subunits, with additional residues on gamma and delta subunits (Kotzyba- Hibert et al., 2004). This six binding-segment-domain model fits quite nicely with the three-dimensional positioning of the homologous residues in AChbinding protein (Brejc et al., 2001). However, little is known about the structural dynamics of the functioning receptor.
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http://dx.doi.org/10.1385/JMN:30:1:13 | DOI Listing |
Int J Mol Sci
January 2025
Sino-American Biological Control Laboratory, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Imidacloprid, a widely used neonicotinoid insecticide, targets insect pests but also affects natural enemies. However, the effects of neonicotinoid insecticides on closely related insects remain unclear. We evaluated the harmful effects of imidacloprid on the phytophagous and predaceous .
View Article and Find Full Text PDFOncogene
January 2025
Department of Pathology, University of California, San Diego, La Jolla, USA.
Smoking plays an underappreciated role in breast cancer progression, increasing recurrence and mortality in patients. Here, we show that S100A8/A9 innate immune signaling is a molecular mechanism that identifies smoking-related breast cancers and underlies their enhanced malignancy. In contrast to acute exposure, chronic nicotine increased tumorigenicity and reprogrammed breast cancer cells to express innate immune response genes.
View Article and Find Full Text PDFAlcohol Clin Exp Res (Hoboken)
January 2025
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
Background: Our previous study demonstrated that alcohol induced the expression of the α4 subunit of nicotinic acetylcholine receptors (nAChRs) in the livers of wild type mice (WT), and that whole-body α4 nAChR knockout mice (α4KO) showed protection against alcohol-induced steatosis, inflammation, and injury. Based on these findings, we hypothesized that hepatocyte-specific α4 nAChRs may directly contribute to the detrimental effects of alcohol on the liver.
Methods: Hepatocyte-specific α4 knockout mice (α4HepKO) were generated, and the absence of α4 nAChR was confirmed through PCR of genomic DNA.
J Agric Food Chem
January 2025
Shanghai Key Laboratory of Chemical Biology & School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. China.
As one of the most significant insecticides, neonicotinoids have played a pivotal role in crop protection and public sanitation. However, the high resistance and bee toxicity of neonicotinoid insecticides have attracted considerable attention. Herein, a series of neonicotinoid compounds with conjugated diene moieties were synthesized through the cascade allylation/isomerization reaction.
View Article and Find Full Text PDFJ Physiol Sci
January 2025
Department of Autonomic Neuroscience, Tokyo Metropolitan Institute for Geriatrics and Gerontology, 35-2 Sakaecho, Itabashi-ku, 173-0015, Tokyo, Japan.
The olfactory bulb receives cholinergic basal forebrain inputs as does the neocortex. With a focus on nicotinic acetylcholine receptors (nAChRs), this review article provides an overview and discussion of the following findings: (1) the nAChRs-mediated regulation of regional blood flow in the neocortex and olfactory bulb, (2) the nAChR subtypes that mediate their responses, and (3) their activity in old rats. The activation of the α4β2-like subtype of nAChRs produces vasodilation in the neocortex, and potentiates olfactory bulb vasodilation induced by olfactory stimulation.
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