PT - JOURNAL ARTICLE AU - Anne Talbodec AU - Nathalie Berkane AU - Virginie Blandin AU - Jean Philippe Breittmayer AU - Emile Ferrari AU - Christian Frelin AU - Paul Vigne TI - Aspirin and Sodium Salicylate Inhibit Endothelin ETA Receptors by an Allosteric Type of Mechanism AID - 10.1124/mol.57.4.797 DP - 2000 Apr 01 TA - Molecular Pharmacology PG - 797--804 VI - 57 IP - 4 4099 - http://molpharm.aspetjournals.org/content/57/4/797.short 4100 - http://molpharm.aspetjournals.org/content/57/4/797.full SO - Mol Pharmacol2000 Apr 01; 57 AB - 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.