Three apparent receptor subtypes for the endothelin/sarafotoxin family

Kloog, Yoel; Bousso-Mittler, D.; Bdolah, Avner; Sokolovsky, Mordechai

doi:10.1016/0014-5793(89)80958-5

Cited by 112 publications

(23 citation statements)

References 16 publications

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“…The specific ET-like immunostaining pattern of endocrine epithelial (for all isopeptides, including the precursor), endothelial (for big-ET-1, ET-1, and ET-2), and smooth muscle (for all forms, but ET-3 only faintly) cells, in addition to the different structures and pharmacological activities, point to various physiological roles of ET peptides in these tissue elements (18,19,31,42). ET-1 is considered to regulate mainly vascular and airway smooth muscle contractility (22,43).…”

Section: Discussionmentioning

confidence: 99%

Endothelin in normal lung tissue of newborn mammals: immunocytochemical distribution and co-localization with serotonin and calcitonin gene-related peptide.

Seldeslagh¹,

Lauweryns²

1993

J Histochem Cytochem.

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We demonstrated immunoreactivity for endothelins (ET)-1, -2, and -3 and for the precursor, big-ET-1, in the pulmonary &se neuroendocrine system (PDNES) of newbom cat, rat, hamster, and mouse. ET-& positive neuroepithelial bodies (NEB) were numerous in the intrapulmonary airways and the alveolar parenchyma. Single neuroendocrine c e l l s (NEC) were less often labeled and mainly localized in the larger bronchi. ET+rea&ve neuronal elements were rarely observed. The intensity and number of iaununostained NEB were highest for ET-3, followed in declining order by big-ET-1, ET-1, and ET-2. ET-like possessing NEB displayed interspecies Merences. We conclude that ET-3 represents a neuroendocrine form of the ET peptide family. NEB expressing several ET isoforms can be grouped into NEB contain-

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Section: Discussionmentioning

confidence: 99%

Endothelin in normal lung tissue of newborn mammals: immunocytochemical distribution and co-localization with serotonin and calcitonin gene-related peptide.

Seldeslagh¹,

Lauweryns²

1993

J Histochem Cytochem.

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“…No specific binding of 125I-labeled ET-1 to parental CHO cells was seen. Our binding data suggest that we have cloned the vascular smooth muscle ET-1 receptor, which has high affinity for both ET-1 and ET-2 but not for ET-3 (12,34,35).…”

Section: Resultsmentioning

confidence: 99%

Cloning and functional expression of a vascular smooth muscle endothelin 1 receptor.

Lin

Kaji

Winkel

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

314

127

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By screening a cDNA library derived from the A10 rat vascular smooth muscle cell line for functional expression in COS cells, we have isolated a high-affinity receptor for endothelin 1 (Kd = 476 pM) and endothelin 2. The affinity of the cloned endothelin receptor for endothelin 3 is >100 times less in A10 cells and in a CHO cell line stably transformed by the endothelin receptor cDNA. The 426-amino acid receptor polypeptide has seven putative hydrophobic transmembrane domains and is presumed to be a member of the family of guanine nucleotide-binding regulatory (G) protein-coupled receptors. Microinjection of in vitro transcripts of the cloned cDNA into CHO cells confers a transient increase in intracellular calcium in response to endothelin 1, indicating that the receptor is functional and couples to the appropriate G protein(s). RNA analysis reveals high expression in rat lung and heart, tissues known to exhibit binding to iodinated endothelin 1.total number of such subtypes and their tissue distribution is unknown.ET binding is followed by an increase in intracellular Ca2+, which is preceded by an increase in inositol phosphates (for review, see refs. 14 and 15). Some work suggests that the actions of ET are sensitive to pertussis toxin and may be mediated by a guanine nucleotide-binding regulatory (G) protein (14, 16), whereas other work indicates that the response to ET is insensitive to pertussis toxin (17-19). Identification and characterization of ET-1 receptors should give insights into the details of signal transduction by ET-1.We report here the cloning, sequencing, ¶ and functional expression of a vascular smooth muscle receptor for ET-1. We establish definitively that it is a subtype that distinguishes ET-1 and ET-2 from ET-3, that it is a seven-transmembranedomain receptor of the G-protein-coupled family, and that it acts through increases in cell Ca2".Endothelin 1 (ET-1), a 21-amino acid peptide secreted by vascular endothelial cells, is one of the most potent vasoconstrictors yet discovered (1). In rats, injection of ET-1 causes prolonged increased mean arterial pressure (2, 3). A correlation has been shown between increased serum ET-1 levels and blood pressure in hypertensive patients (4, 5). These results suggest a possible pathologic role for circulating ET-1 in the etiology of essential hypertension and the potential therapeutic benefits of endothelin (ET) antagonists for the treatment of this disease.ET-1, endothelin 2 (ET-2), endothelin 3 (ET-3), and vasoactive intestinal contractor (or endothelin-,3) are members of a family of related mammalian peptides (6)(7)(8). The structures of these peptides are unique among hormones produced by mammalian species. All are 21-amino acid peptides with two disulfide bridges. The mammalian ETs closely resemble the sarafotoxin class of snake venoms, which produce coronary vasoconstriction (9). They also exhibit homology to a-scorpion toxin, one of a family of toxins known to bind to and activate the voltage-gated Na' channel. This similarity to inse...

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“…113,114 The chemical structure of the endothelins is closely related to neurotoxins (sarafotoxins) produced by scorpions and snakes. [115][116][117] Factors modulating the expression of ET-1 are shearstress, adrenaline, angiotensin II, thrombin, inflammatory cytokines (tumor necrosis factor-␣, interleukin-1 and -2), transforming growth factor-␤, and hypoxia. [118][119][120][121][122][123][124][125][126][127][128][129][130] ET-1 is metabolized by a neutral endopeptidase, which also cleaves natriuretic peptides.…”

Section: Endothelinmentioning

confidence: 99%

Working under pressure: the vascular endothelium in arterial hypertension

et al. 2000

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The vascular endothelium synthesizes and releases a spectrum of vasoactive substances like nitric oxide (NO) and endothelin (ET). In hypertension, the delicate balance of endothelium-derived factors is disturbed. ET acts as the natural counterpart to endothelium-derived NO, which exerts vasodilating, antithrombotic, and antiproliferative effects, and inhibits leukocyte-adhesion to the vascular wall. Besides its blood pressure rising effect also in man, ET induces vascular and myocardial hypertrophy, which are independent risk factors for cardiovascular morbidity and mortality. The derangement of endothelial function in hypertension is likely to be caused in part by genetic factors, but also due to elevated blood pressure itself. Due to its position between blood pressure and smooth muscle cells responsible for peripheral resistance, the endothelium is thought to be both target and mediator of arterial hypertension. Oxi-

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Three apparent receptor subtypes for the endothelin/sarafotoxin family

Cited by 112 publications

References 16 publications

Endothelin in normal lung tissue of newborn mammals: immunocytochemical distribution and co-localization with serotonin and calcitonin gene-related peptide.

Endothelin in normal lung tissue of newborn mammals: immunocytochemical distribution and co-localization with serotonin and calcitonin gene-related peptide.

Cloning and functional expression of a vascular smooth muscle endothelin 1 receptor.

Working under pressure: the vascular endothelium in arterial hypertension

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