Aspirin and sodium salicylate inhibit endothelin ETA receptors by an allosteric type of mechanism.

Article Details

Citation

Copy to clipboard

Talbodec A, Berkane N, Blandin V, Breittmayer JP, Ferrari E, Frelin C, Vigne P

Aspirin and sodium salicylate inhibit endothelin ETA receptors by an allosteric type of mechanism.

Mol Pharmacol. 2000 Apr;57(4):797-804.

PubMed ID

10727528 [ View in PubMed

]

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 Ca(2+) 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 (125)I-ET-1 binding to recombinant rat ETA receptors. Salicylic acid promotes dissociation of (125)I-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 (125)I-ET-1 to ETA receptors. Salicylates do not promote dissociation of (125)I-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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Acetylsalicylic acid	Endothelin-1 receptor	Protein	Humans	Unknown	Inhibitor	Details