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- W2169002037 endingPage "2625" @default.
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- W2169002037 abstract "As for other peptides such as bradykinin, neurokinins and angiotensins, peptide antagonists for endothelin-1 (ET-1) have been early on developed towards the pharmacological characterization of both ETA and ETB receptors. Interestingly, unlike the previously mentioned three peptides, receptors for ET-1 were cloned and purified prior to the report of ETA and ETB receptor antagonists such as BQ-123 and BQ-788. The availability of such pharmacological tools and the use of molecular approaches have certainly fast-tracked the development of non-peptide ET receptor antagonists for clinical applications. Albeit rapid degradation by gastric enzymes and short halflife in plasma of peptide receptor antagonists limit their use in clinical settings, those molecules have been of importance in the identification of mediators and modulators of ET-1 induced properties in vitro and in vivo, as described further in this review. Peptide antagonists acting selectively or, with equivalent affinities against ETA and ETB receptors were reported prior to the advent of clinically relevant non-peptide blockers such as Bosentan. Confounding mechanisms involving, for example, the endogenous modulators nitric oxide and prostacyclin as well as allosteric interactions between ET receptor types, have also been clarified with the use of peptide antagonists for endothelins. Finally, peptide antagonists were also used to identify the precise pharmacology of ET-1 precursors such as big-endothelin-1 and ET-1 (1-31). The present review will thus attempt to summarize the knowledge to date and future perspectives related to use of peptide antagonists targeting endothelin receptors in physiological and pathological settings. Keywords: Endothelin-1, antagonists, ETA and ETB receptors, Streptomyces misakiensis, amino acid isoforms, disulfide bonds, pulmonary hypertension, sulfamethoxazole, subarachnoid hemorrhage, Salicylic acid, Neurogenesis, Hippocampus, Neuroblast, Rostral migratory stream, brain tumor stem cell, NG2, Ependyma, Stem cell, dentate gyrus, subgranular zone, cytokine, PSA-NCAM, Ki67, Interleukin" @default.
- W2169002037 created "2016-06-24" @default.
- W2169002037 creator A5012952538 @default.
- W2169002037 creator A5042038598 @default.
- W2169002037 creator A5063891264 @default.
- W2169002037 date "2011-08-01" @default.
- W2169002037 modified "2023-10-18" @default.
- W2169002037 title "Peptide and Non-peptide Antagonists Targeting Endothelin Receptors in Physiology and Pathology" @default.
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