The ability of Bordetella heat-labile toxin (HLT) to contract various types of cells in culture was examined. HLT from B. parapertussis induced contraction of cultured smooth muscle cells from trachea, intestine, uterus and vas deferens as well as from aorta. The time required for contraction decreased as the dose of B. parapertussis HLT increased from 3 to 100 MID/ml. Upon exposure of cells to concentrations of toxin greater than 100 MID/ml, at least 2 hr was required for contraction. HLT from B. parapertussis did not affect cultured cardiac or skeletal muscle cells within 8 hr after the exposure to HLT (100 MID/ml). No effect on other types of primary culture cells or established cells such as Chinese hamster ovary (CHO) cells has been described. These data indicate that the primary target cells for HLT might be smooth muscle cells.
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http://dx.doi.org/10.1111/j.1348-0421.1992.tb02063.x | DOI Listing |
Arterioscler Thromb Vasc Biol
January 2025
British Heart Foundation Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, United Kingdom. (M.W., M.F., R.O., L.S., M.M., C.M.S.).
Background: The ECM (extracellular matrix) provides the microenvironmental niche sensed by resident vascular smooth muscle cells (VSMCs). Aging and disease are associated with dramatic changes in ECM composition and properties; however, their impact on the VSMC phenotype remains poorly studied.
Methods: Here, we describe a novel in vitro model system that utilizes endogenous ECM to study how modifications associated with age and metabolic disease impact the VSMC phenotype.
ACS Pharmacol Transl Sci
January 2025
Laboratory of Integrative Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
The accumulation of ceramides and related metabolites has emerged as a pivotal mechanism contributing to the onset of age-related diseases. However, small molecule inhibitors targeting the ceramide synthesis pathway for clinical use are currently unavailable. We synthesized a safe and orally bioavailable inhibitor, termed ALT-007, targeting the rate-limiting enzyme of ceramide synthesis, serine palmitoyltransferase (SPT).
View Article and Find Full Text PDFACS Pharmacol Transl Sci
January 2025
Department of Medicinal Chemistry and Institute for Translational Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Opioid agonist ligands bind opioid receptors and stimulate downstream signaling cascades for various biological processes including pain and reward. Historically, before cloning the receptors, muscle contraction assays using isolated organ tissues were used followed by radiolabel ligand binding assays on native tissues. Upon cloning of the opioid G protein-coupled receptors (GPCRs), cell assays using transfected opioid receptor DNA plasmids became the standard practice including S-GTPγS functional and cAMP based assays.
View Article and Find Full Text PDFTheranostics
January 2025
State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Lower vertebrates and some neonatal mammals are known to possess the ability to regenerate cardiomyocyte and fully recover after heart injuries within a limited period. Understanding the molecular mechanisms of heart regeneration and exploring new ways to enhance cardiac regeneration hold significant promise for therapeutic intervention of heart failure. Sphingosine 1-phospahte receptor 1 (S1PR1) is highly expressed in cardiomyocytes and plays a crucial role in heart development and pathological cardiac remodeling.
View Article and Find Full Text PDFTher Clin Risk Manag
January 2025
Departments of Medicine and Cardiology, Westchester Medical Center and New York Medical College, Valhalla, NY, USA.
Pulmonary arterial hypertension (PAH) is a rare and potentially fatal condition characterized by progressive increases in blood pressure in the arteries of the lungs. Oral selexipag, approved by the Food and Drug Administration (FDA) in 2015 for the treatment of PAH, targets prostacyclin receptors on pulmonary arterial vascular smooth muscle and endothelial cells to improve blood flow through the lungs and reduce pulmonary vascular resistance. Oral selexipag is effective, but may be discontinued due to factors like side effects, emergency conditions, or inability to take oral medication, potentially leading to severe adverse events, such as rebound pulmonary hypertension and right heart failure.
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