Endothelin Receptor Subtypes and Tissue Distribution

Pollock, David M.

doi:10.1007/978-1-4757-2783-8_1

Cited by 11 publications

(11 citation statements)

References 122 publications

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“…However, some tissues express ET B receptor predominantly, which seems to suggest that ET B receptor may also play a pathophysiological role [17]. Thus, ET Aselective or ET B -selective antagonists could potentially have their unique utilities.…”

Section: Introductionmentioning

confidence: 99%

Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: ex vivo and in vivo studies

et al. 2002

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Endothelins (ETs), 21-amino-acid peptides involved in the pathogenesis of various diseases, bind to ET(A) and ET(B) receptors to initiate their effects. Based on the same core structure, we have developed four small-molecule ET receptor antagonists, ABT-627 (atrasentan), ABT-546, A-182086 and A-192621, which exhibit differences in selectivity for ET(A) and ET(B) receptors. In this report, we compare the efficacy, potency and pharmacokinetic properties of these four antagonists, including potency in inhibiting ET-1- or Sarafotoxin 6c-induced vessel constriction in isolated arteries and efficacy in antagonizing ET-1-, big ET-1- or Sarafotoxin 6c-induced pressor responses in rats.

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Section: Introductionmentioning

confidence: 99%

Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: ex vivo and in vivo studies

et al. 2002

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“…All of endothelin’s effects are elicited by binding to specific G-protein coupled receptors Endothelin Receptor A (ETRA) (Arai, Hori, Aramori, Ohkubo, & Nakanishi, 1990) and Endothelin Receptor B (ETRB) (Sakurai et al, 1990). ETRA and ETRB demonstrate considerable variability in the distribution between different tissues and among species (Pollock, 1998). Human and rat renal tubular cells, vascular smooth muscle cells, glomerular mesangial cells and many other cell types express substantial levels of both ETRA and ETRB (Orth et al, 2000; Kohan et al, 2011; Bouallegue, Daou, & Srivastava, 2007; Sorokin, 2011).…”

Section: Endothelin Signaling and Control Of Blood Pressurementioning

confidence: 99%

Inhibition of ENaC by Endothelin-1

Sorokin

Staruschenko

2015

Hormones and Transport Systems

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The amiloride-sensitive epithelial Na+ channel (ENaC) is a key player in the regulation of Na+ homeostasis. Its functional activity is under continuous control by a variety of signaling molecules including bioactive peptides of endothelin family. Since ENaC dysfunction is causative for disturbances in total body Na+ levels associated with abnormal regulation of blood volume, blood pressure, and lung fluid balance, the uncovering the molecular mechanisms of inhibitory modulation or inappropriate activation of ENaC is crucial for the successful treatment of a variety of human diseases including hypertension. The precise regulation of ENaC is particularly important for normal Na+ and fluid homeostasis in organs where endothelins are known to act: kidneys, lung and colon. Inhibition of ENaC by endothelin-1 (ET-1) has been established in renal cells and several molecular mechanisms of inhibition of ENaC by ET-1 are proposed and will be reviewed in this chapter.

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“…Produced through a process of proteolytic cleavages of a precursor to yield the active moiety, ET‐1 acts through ET A or ET B receptor subtypes 1 . ET A receptors are present on vascular smooth muscle and are responsible for the vasoconstrictor properties of ET‐1 2 . ET B receptors are present on a variety of cell types, including vascular endothelial and renal tubular cells 2 .…”

Section: Introductionmentioning

confidence: 99%

“…ET A receptors are present on vascular smooth muscle and are responsible for the vasoconstrictor properties of ET‐1 2 . ET B receptors are present on a variety of cell types, including vascular endothelial and renal tubular cells 2 . Nitric oxide is produced, along with L ‐citrulline, via the action of NO synthase (NOS) using the substrates L ‐arginine and O 2 .…”

Section: Introductionmentioning

confidence: 99%

Chronic Studies on the Interaction Between Nitric Oxide and Endothelin in Cardiovascular and Renal Function

Pollock

1999

Clin Exp Pharma Physio

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1. Chronic inhibition of nitric oxide synthase (NOS) results in a persistent hypertension, while chronic blockade of endothelin ETA receptors has little effect on arterial pressure. These findings indicate that nitric oxide (NO) plays a more significant role than ET-1 in the long-term maintenance of arterial pressure. 2. Although endothelin (ET) appears to contribute to the hypertension in the early stages of NOS inhibition, blockade of either ETA or both ETA and ETB receptors has only a minor effect on the hypertension beyond the initial 2 weeks of NOS inhibition. 3. Endothelin may play a role in vascular lesion development associated with NOS inhibition, at least within the kidney, which may be related to angiotensin II activity. 4. The processes involved in the hypertension associated with chronic NOS inhibition appear to be dynamic and may include an evolution of ET-1 action. Variability in results from different laboratories may be related to genetic factors and choice of pharmacological agents.

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Endothelin Receptor Subtypes and Tissue Distribution

Cited by 11 publications

References 122 publications

Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: ex vivo and in vivo studies

Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: ex vivo and in vivo studies

Inhibition of ENaC by Endothelin-1

Chronic Studies on the Interaction Between Nitric Oxide and Endothelin in Cardiovascular and Renal Function

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