| Aspirin and sodium salicylate inhibit endothelin ETA receptors by an allosteric type of mechanism. | |
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MedLine Citation:
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PMID: 10727528 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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A Talbodec; N Berkane; V Blandin; J P Breittmayer; E Ferrari; C Frelin; P Vigne |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular pharmacology Volume: 57 ISSN: 0026-895X ISO Abbreviation: Mol. Pharmacol. Publication Date: 2000 Apr |
Date Detail:
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Created Date: 2000-05-04 Completed Date: 2000-05-04 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0035623 Medline TA: Mol Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 797-804 Citation Subset: IM |
Affiliation:
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Institut de Pharmacologie Moléculaire et Cellulaire du Centre National de la Recherche Scientifique, Valbonne, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Allosteric Regulation
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drug effects Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology* Aorta Aspirin / pharmacology* Biological Transport / drug effects Calcium / metabolism Cells, Cultured Drug Synergism Endothelin-1 / metabolism Humans Mammary Arteries / drug effects Muscle Contraction / drug effects Rats Receptors, Endothelin / antagonists & inhibitors*, metabolism Sodium Salicylate / pharmacology* Sulfonamides / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents, Non-Steroidal; 0/Endothelin-1; 0/Receptors, Endothelin; 0/Sulfonamides; 147536-97-8/bosentan; 50-78-2/Aspirin; 54-21-7/Sodium Salicylate; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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