Discovery and Development of an Endothelin a Receptor-Selective Antagonist PD 156707

Doherty, Annette M.; Uprichard, Andrew

doi:10.1007/0-306-47384-4_5

Cited by 5 publications

(2 citation statements)

References 95 publications

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“…12-14 ET is a ten-fold more potent vasoconstrictor than angiotensin II and has extremely long-lasting pressor effects. 4 Severe sepsis is characterized by an increase in cardiac output, general vasodilatation and/or hypotension. These cardiovascular changes are mediated by endogenous vasodilatators like nitric oxide and ANP and vasoconstrictors like ET.…”

Section: Discussionmentioning

confidence: 99%

Elevated plasma levels of endothelin are associated with the severity of sepsis and presence of shock in contrast to the levels of atrial natriuretic peptide

Beishuizen

Götz

Kip

et al. 1992

Mediators of Inflammation

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Immunoreactive endothelin (ETi) and atrial natriuretic peptide (ANPi) blood levels were measured by radioimmunoassay in patients with clinically defined sepsis. The interaction between these two peptides and their relation to circulatory shock and mortality were studied. All septic patients (n = 16) had significantly higher ETi (22.3 ± 11.1 pg/ml) and ANPi (398.3 ± 154.3 pg/ml) plasma concentrations compared to control subjects (ETi, 4.1 ± 1.2; ANPi, 59.1 ± 14.8 pg/ml; n = 13). ETi levels followed the severity of illness according to the APACHE II scoring system and were higher in patients who did not survive. ETi levels were significantly higher in the presence of shock and bacteraemia. Furthermore, ETi correlated well with plasma lactate (r = 0.83, p < 0.05), but not with renal function. ANPi levels did not show correlation with any of these determinants. Serial blood sampling, six consecutive days after admission, showed that ETi levels gradually decreased in normotensive patients in contrast to patients with septic shock. ANPi levels did not show systematic changes in time, and no relationship was observed between ETi and ANPi levels. These results suggest that plasma ETi levels are indicative for disease severity and might have prognostic significance. The role of ANPi during sepsis remains to be eludicated.

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Section: Discussionmentioning

confidence: 99%

Elevated plasma levels of endothelin are associated with the severity of sepsis and presence of shock in contrast to the levels of atrial natriuretic peptide

Beishuizen

Götz

Kip

et al. 1992

Mediators of Inflammation

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“…[15][16][17] The developed photoprobe, termed ET A -Cy5.5 (2; Figure 1), is based on PD 156707, a potent ET receptor antagonist with high affinity and ET A selectivity. [18][19][20][21] The tracer was synthesized by reaction of Cy5.5 Nhydroxysuccinimidyl-(NHS-) ester with amino-precursor 1 (see Figure 1). 22 In this study, we examined the biodistribution of the tracer in wild-type CD-1 mice to assess the applicability of the probe to image ET A R expression in vivo.…”

mentioning

confidence: 99%

Biodistribution of a Nonpeptidic Fluorescent Endothelin a Receptor Imaging Probe

Höltke¹,

Waldeck²,

Kopka³

et al. 2009

Mol Imaging

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Biodistribution studies are essential for understanding the biologic behavior of novel fluorochrome-based molecular imaging agents. In this study, the biodistribution of a recently developed fluorescent imaging probe with high affinity to the endothelin A (ET(A)) receptor was evaluated by fluorescence reflectance imaging (FRI). CD-1 mice were injected with 2 nmol of the probe intravenously and sacrificed at various time points. Tissue samples of the heart, spleen, lung, kidneys, liver, brain, and muscle were removed and imaged by FRI. Initially, the signal intensity (SI) was highest in lung, kidney, and liver tissue, followed by the heart, whereas spleen, muscle, and brain showed the lowest SI. In the kidneys, the SI decreased rapidly. In the heart, an initial SI increase was observed, followed by SI attenuation, whereas in the lung, the SI steadily increased. Competition experiments showed a significant (p < .005) degree of specific binding in the heart, with a reduction in SI of > 50%. In conclusion, FRI allows us to perform biodistribution studies of novel fluorescent tracers. The developed imaging probe can be exploited to image ET A receptor expression ideally 30 minutes to 3 hours after injection.

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Vascular Injury Biomarkers

Zabka¹,

Bendjama²

2016

Drug Discovery Toxicology

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Discovery and Development of an Endothelin a Receptor-Selective Antagonist PD 156707

Cited by 5 publications

References 95 publications

Elevated plasma levels of endothelin are associated with the severity of sepsis and presence of shock in contrast to the levels of atrial natriuretic peptide

Elevated plasma levels of endothelin are associated with the severity of sepsis and presence of shock in contrast to the levels of atrial natriuretic peptide

Biodistribution of a Nonpeptidic Fluorescent Endothelin a Receptor Imaging Probe

Vascular Injury Biomarkers

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