In representatives of class of birds (pigeons Columba livia) using electrophysiological methods for the first time there was performed analysis of effects of microinjections into the hypothalamic ventrolateral preoptical area (VLPA) of antagonists of the adenosine A(2A) type receptors on the sleep-wale cycle under natural conditions and on realization of somnogenic effect of Heat shock protein 70 kDa (Hsp70). The following has been established: 1) microinjections of adenosine A(2A) receptors antagonist (8-(3-Chlorostyryl) caffeine (ChC)) into VLPA at the beginning of inactive phase of the 24-h period dose-dependently increase wakefulness and suppress sleep; 2) microinjections of Hsp70 into VLPA produce somnogenic effect manifested as an increase of the total time of slow sleep (SS) and enhancement of mechanisms of initiation and maintenance of SS; 3) block of adenosine A(2A) receptors by ChC suppresses the Hsp70-induced SS. The obtained data indicate participation of adenosine A(2A) receptors located in VLPA in modulation of the sleep-wake cycle under natural conditions and in realization of somnogenic effect of Hsp70 in pigeons. A hypothesis is put forward that the somnogenic action of Hsp70 is mediated by modulating effect of this chaperone on function of adenosine proteins-receptors.
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Acta Pharmacol Sin
January 2025
Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Joint International Research Laboratory of Sleep, Fudan University, Shanghai, 200032, China.
Adenosine A receptor (AR) plays a pivotal role in the regulation of sleep-wake behaviors. We previously reported an AR selective antagonist compound 38 with an IC value of 29.0 nM.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
CEITEC─Central European Institute of Technology, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic.
All-atom molecular dynamics simulations are powerful tools for studying cell membranes and their interactions with proteins and other molecules. However, these processes occur on time scales determined by the diffusion rate of phospholipids, which are challenging to achieve in all-atom models. Here, we present a new all-atom model that accelerates lipid diffusion by splitting phospholipid molecules into head and tail groups.
View Article and Find Full Text PDFEur J Neurosci
January 2025
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
In corticostriatal nerve terminals, glutamate release is stimulated by adenosine via A receptors (ARs) and simultaneously inhibited by endocannabinoids via CB receptors (CBRs). We previously identified presynaptic AR-CBR heterotetrameric complexes in corticostriatal nerve terminals. We now explored the possible functional interaction between ARs and CBRs in purified striatal GABAergic nerve terminals (synaptosomes) and compared these findings with those on the release of glutamate.
View Article and Find Full Text PDFCell Rep
January 2025
Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. Electronic address:
Macrophages play a crucial role in immune responses and undergo metabolic reprogramming to fulfill their functions. The tetramerization of the glycolytic enzyme pyruvate kinase M2 (PKM2) induces the production of the anti-inflammatory cytokine interleukin (IL)-10 in vivo, but the underlying mechanism remains elusive. Here, we report that PKM2 activation with the pharmacological agent TEPP-46 increases IL-10 production in LPS-activated macrophages by metabolic reprogramming, leading to the production and release of ATP from glycolysis.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Atherothrombosis Research Centre/Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 451 10 Ioannina, Greece.
Ticagrelor, a reversible platelet P2Y receptor antagonist, exerts various pleiotropic actions, some of which are at least partially mediated through adenosine. We studied the ticagrelor and adenosine effect on the angiogenic properties of progenitor CD34-derived endothelial colony-forming cells (ECFCs). Angiogenesis studies were performed in vitro using capillary-like tube formation and spheroid-based angiogenesis assays.
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