Different effects of pulsed electromagnetic field (PEMF) exposure on brain tissue have been described in pre-clinical models and in clinical settings. Nevertheless, the mechanism of action and the possible interaction with membrane receptors such as adenosine receptors (ARs) has not been investigated. The present study focused on the effect of PEMFs on A1 and A2A ARs in the rat cerebral cortex and cortical neurons. Affinity and density of ARs were evaluated by means of saturation binding experiments while mRNA expression was investigated through retro-transcription polymerase chain reaction (RT-PCR). PEMF treatment of the intact rat cerebral cortex or cortical neurons at 1.5 mT mediated a transient and significant increase in A2A ARs after 4 h (2.0-fold increase) and 6 h (1.4- and 1.8-fold increase, respectively) of exposure. In addition, PEMF treatment of the rat cerebral cortex and rat cortical neurons at 3 mT upregulated A2A ARs after 2 h (2.0- and 2.2-fold increase, respectively) and 4 h (1.6- and 1.9-fold increase, respectively). The treatment of rat cortex membranes with PEMFs at 1.5 and 3 mT induced an increase in A2A AR density after 2 h (1.9- and 2.2-fold increase, respectively) and was constant at all incubation times investigated. In rat cortical neurons, mRNA levels of A1 and A2A ARs were not affected by PEMF exposure for the times and intensities used. These results suggest that PEMF treatment has different biological effects in whole organs or cells in comparison with isolated membranes.
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Bioorg Med Chem
December 2024
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; Future Medicine Co., Ltd, 54 Changup-ro, Sujeong-gu, Seongnam, Gyeonggi-do 13449, Republic of Korea. Electronic address:
This study investigated the impact of conformation on the binding affinity of carbanucleosides to A and A adenosine receptors (ARs). A series of nucleosides, including saturated, unsaturated, North (N)-methano, and South (S)-methanocarbanucleosides was prepared, and their binding affinities to AAR and AAR were assessed. Biological evaluations revealed that all synthesized (S)-methanocarbanucleosides had negligible binding to both receptors, and most (N)-methanocarbanucleosides exhibited high binding affinities.
View Article and Find Full Text PDFBiol Psychiatry
October 2024
Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee; Vanderbilt Center for Addiction Research, Vanderbilt University School of Medicine, Nashville, Tennessee; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee; Department of Neurobiology, University of Massachusetts Chan Medical School, Worcester, Massachusetts. Electronic address:
Mol Cancer Ther
November 2024
EMD Serono, Billerica, Massachusetts.
While A2A adenosine receptor (AR) was considered as a major contributor to adenosine-mediated immunosuppression, A2B, having the lowest affinity to adenosine, has also emerged as a potential contributor to tumor promotion. Therefore, in adenosine-rich tumor microenvironment (TME), where A2B could be complementary and/or compensatory to A2A, simultaneous targeting of A2A and A2B ARs can provide higher potential for cancer immunotherapy. We developed M1069-a highly selective dual antagonist of the A2A and A2B AR.
View Article and Find Full Text PDFMolecules
July 2024
School of Pharmacy, Medicinal Chemistry Unit, ChIP, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy.
Cancer, a complex array of diseases, involves the unbridled proliferation and dissemination of aberrant cells in the body, forming tumors that can infiltrate neighboring tissues and metastasize to distant sites. With over 200 types, each cancer has unique attributes, risks, and treatment avenues. Therapeutic options encompass surgery, chemotherapy, radiation therapy, hormone therapy, immunotherapy, targeted therapy, or a blend of these methods.
View Article and Find Full Text PDFPharmaceutics
October 2023
Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy.
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