@article {Talbodec797, author = {Anne Talbodec and Nathalie Berkane and Virginie Blandin and Jean Philippe Breittmayer and Emile Ferrari and Christian Frelin and Paul Vigne}, title = {Aspirin and Sodium Salicylate Inhibit Endothelin ETA Receptors by an Allosteric Type of Mechanism}, volume = {57}, number = {4}, pages = {797--804}, year = {2000}, doi = {10.1124/mol.57.4.797}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Aspirin is a commonly used drug with a wide pharmacological spectrum including antiplatelet, anti-inflammatory, and neuroprotective actions. This study shows that aspirin and sodium salicylate, its major blood metabolite, reverse contractile actions of endothelin-1 (ET-1) in isolated rat aorta and human mammary arteries. They also prevent the intracellular Ca2+ mobilizing action of ET-1 in cultured endothelial cells but not those of neuromedin B or UTP. Inhibition of the actions of ET-1 by salicylates is apparently competitive. Salicylates inhibit 125I-ET-1 binding to recombinant rat ETA receptors. Salicylic acid promotes dissociation of125I-ET-1 ETA receptor complexes both in the absence and the presence of unlabeled ET-1. It has no influence on the rate of association of 125I-ET-1 to ETA receptors. Salicylates do not promote dissociation of 125I-ET-1 ETB receptor complexes. Salicylates potentiate relaxing actions of receptor antagonists such as bosentan. It is concluded that salicylates are allosteric inhibitors of ETA receptors. The results also suggest that: 1) irreversible ET-1 binding probably limits actions of receptor antagonists in vivo, and 2) an association of salicylates and ETA receptor antagonists should be used to evaluate the physiopathological role of ET-1 and may be of therapeutic interest in the treatment of ischemic heart disease.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/57/4/797}, eprint = {https://molpharm.aspetjournals.org/content/57/4/797.full.pdf}, journal = {Molecular Pharmacology} }