China
Africa
Explore chapters and articles related to this topic
Endothelins in the Lung
Published in Sami I. Said, Proinflammatory and Antiinflammatory Peptides, 2020
Peter J. Henry, Roy G. Goldie, Douglas W. P. Hay
Recently a number of groups have reported that the ability of ET receptor antagonists, such as BQ-123, to inhibit functional responses mediated by ET receptors is dependent on the agonist used (89–91). In some cases this has been used as evidence for the existence of novel ETA and ETB receptor subtypes (92,93). For example, atypical ETa and ETB receptors have been suggested to mediate the contractile actions of ET-1 in guinea pig hilar bronchus (94) and rabbit trachea (92). However, due to the pitfalls associated with the classification of receptor subtypes based solely on functional data (95), any extension to the current ET receptor subclassification requires additional support from structural, operational, and signal transduction data (96). Indeed, recent studies of fibroblasts expressing cloned ETA receptors indicate that the differential sensitivities of ET-1 and ET-3 to blockade by BQ-123 is an intrinsic property of activated ETA receptors and that there is no need to postulate the existence of new ETA receptor isoforms (97). For a general discussion of atypical endothelin receptors, the reader is directed to a recent review by Bax and Saxena (98).
Modulating barriers of tumor microenvironment through nanocarrier systems for improved cancer immunotherapy: a review of current status and future perspective
Published in Drug Delivery, 2020
Huanrong Lan, Wei Zhang, Ketao Jin, Yuyao Liu, Zhen Wang
Vasoconstrictive endothelin-1 (ET1) and its ETA receptor, by which ET-1 mediates vasoconstriction, are also present in cancer cells to preserve the tumor vessel contractile signal. The frequency of expression of ET1 and ETA in tumor vessels was 13 and 5 times greater than that of regular vessels balanced in scale, accordingly (Kowalczyk et al., 2015). BQ123, a selective antagonist against ETA, can prevent ET1-ETA signaling, stimulate dilation of the tumor vessels, and trigger tumor-specific blood flow growth. The BQ123-induced boost in the blood flow increased the distribution of free drugs to tumors following a rise in IFP (Zamora et al., 1993). Furthermore, it has been shown that BQ123 could promote the levels of photothermal nanomedicine by about 100 nm for successful photothermal treatment of tumors (Zamora et al., 1993). A few inflammation variables, including such bradykinin, which can dilate vessels, also could boost tumor perfusion directly. In our previous research, captopril, a commonly used hypotensor in clinics, has been shown to dilate tumor blood vessels by growing the bradykinin expression and also growing the permeability of tumor vessels to increase the distribution of nanomedicine for cancer treatment (Zhang et al., 2017a).
The effect of endothelin receptor antagonists in the endotoxin-induced uveitis rabbit model*
Published in Cutaneous and Ocular Toxicology, 2018
Emine Esra Karaca, Feyzahan Uzun, Ergin Dileköz, Gökçe Sevim Öztürk Fincan, Sevim Ercan, Oğuz Kul, Emin Ümit Bağrıaçık, Meral Or
Selective ETA receptor antagonists such as BQ123 prevent ET-1 binding to receptors in vascular smooth muscle. In a study conducted by Ihara et al.18, by using BQ123, anaesthetized rats did not completely lose the vasoconstriction effect of ET-1 in the aortic smooth muscle, ETB receptors could also play a role in vasoconstriction. While vasoconstrictor effect in rats was provided by ETA and ETB receptors, BQ123 totally inhibited ET-1-dependent renal vasoconstriction in pigs and rabbits31. Because of the different distribution of ETA and ETB receptors among species and different responses to receptor antagonists, there is no definite conclusion to be expected with the use of these agents. For example, Maggi et al.32 have shown that the contraction effect in the rabbit pulmonary artery is mediated by ETB receptors and BQ123 could not inhibit this contraction. Furthermore, the NO and PG secretory effect of ETB receptors on vascular endothelium can not be inhibited by BQ123.
Selective endothelin A receptor antagonism in patients with proteinuric chronic kidney disease
Published in Expert Opinion on Investigational Drugs, 2021
Michele Provenzano, Michele Andreucci, Carlo Garofalo, Roberto Minutolo, Raffaele Serra, Luca De Nicola
Early human studies were designed to test the effect of acute infusion of ERA in modifying renal perfusion and renal damage [40,41]. Interestingly, a study enrolling CKD patients with glomerulonephritis, showed that infusion of BQ-123 on top of maximum-tolerated RAASi caused a fall in BP and proteinuria while determining an increase in renal blood flow [42]. In these patients, the reduction in proteinuria was greater if ERA was added to patients receiving dual RAASi blockade than those treated with either Angiotensin II Receptor Blockers (ARB) or ACEi [43].