[Ala1,3,11,15]endothelin-1 analogs with ETB agonistic activity

Saeki, Toshihiko; Ihara, Masaki; Fukuroda, Takahiro; Yamagiwa, Miho; Yano, Mitsuo

doi:10.1016/0006-291x(91)91367-l

Cited by 159 publications

(107 citation statements)

References 18 publications

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“…A differential distribution of ET receptor subtypes has also been demonstrated in the human foetal heart and porcine pulmonary tissues (Nakamichi et al, 1991 (Hemsen et al, 1990;van Papendorp et al, 1991) (Takayanagi et al, 1991;Namiki et al, 1992 (Ihara et al, 1991;Fukurodoa et al, 1992;Moreland et al, 1992;Panek et al, 1992). Studies on mammalian isolated blood vessels indicate that ETA receptors mediate the ET-induced vasoconstriction of arterial smooth muscle whereas ETB receptors are responsible for the contractile response in veins (Moreland et al, 1992).…”

Section: Discussionmentioning

confidence: 97%

“…The selective (ETA) subtype exhibits a high affinity for ET-l and ET-2, and -1000 fold lower affinity for ET-3, whereas the non-selective (ETB) receptor subtype binds all three isoforms with a similar affinity. A number of ETA and ETB selective peptide sequences have been identified, including the cyclic pentapeptide BQ123, a potent ETA antagonist (Ihara et al, 1991), and BQ3020, an alanine substituted truncated ET-1 analogue which is a potent ETB agonist (Saeki et al, 1991;Ihara et al, 1992). ETB type binding sites may also be distinguished on the basis of their high affinity for the agonists, sarafotoxin 6c (Williams et al, 1991) and [Ala3"1'8Nle7]-ET-l (Hunt et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

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Differential localization of endothelin ET_a and ET_B binding sites in human placenta

Rutherford

Wharton

McCarthy

et al. 1993

British J Pharmacology

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1 The localization and differential distribution of endothelin (ET) receptor subtypes (ETA and ETB) was investigated in sections of human placenta by use of quantitative in vitro autoradiography and receptor selective ligands.2 Specific, high density ['251]-ET-1 binding sites were localized to the decidua and foetal membranes as well as to arteries and veins in the chorionic plate and throughout the villous tree. Moderate to low density binding was found in the extravillous and villous trophoblast respectively. 6 ET may have a local autocrine or paracrine role in the placenta, acting via specific receptors to influence foetoplacental blood flow and other aspects of placental function.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Differential localization of endothelin ET_a and ET_B binding sites in human placenta

Rutherford

Wharton

McCarthy

et al. 1993

British J Pharmacology

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“…ETA receptors preferentially bind ET-1 over ET-3 (Arai et al, 1990) and are present on vascular smooth muscle cells (Lin et al, 1991) where their stimulation leads to vasoconstriction. The ETB receptors are non-selective for ET-1 and ET-3 (Sakurai et al, 1990) and are located on endothelial cells where their stimulation leads to vasodilatation (Saeki et al, 1991;Takayanagi et al, 1991). The ETc receptor binds ET-3 with a higher affinity than ET-1 and was recently cloned from Xenopus melanophores (Karne et al, 1993).…”

Section: Methodsmentioning

confidence: 99%

Evidence for a differential location of vasoconstrictor endothelin receptors in the vasculature

Moreland¹,

McMullen

Abboa-Offei

et al. 1994

British J Pharmacology

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1 There are at least two subtypes of vascular endothelin (ET) receptors. Stimulation of the ETA receptors on vascular smooth muscle cells leads to vasoconstriction, whereas activation of the ETB receptors on endothelial cells elicits vasodilatation. Several reports in the literature have suggested the presence of a vasoconstrictor non-ETA receptor on vascular smooth muscle which has pharmacological similarities to the ETB receptor. The present study was undertaken to determine the location of this ETB-like receptor within the vascular system. 2 Fourteen vascular smooth muscle preparations from six species were used to determine the effect of the ETA receptor antagonist, BQ-123, on concentration-response curves elicited by ET-1 and the ability of the ETB receptor agonist, sarafotoxin S6c, to cause contraction. The vessels fell into two categories. One group was sensitive to BQ-123 and insensitive to sarafotoxin S6c and, thus, probably contained ETA receptors. The other group, with vasoconstrictor ETB-like receptors, was insensitive to BQ-123 and sensitive to sarafotoxin S6c. 3 Vessels from cynomolgus monkeys, when studied in vitro, appeared to contain primarily ETA receptors, although the potency of BQ-123 was quite variable, suggesting the possibility of ETA receptor subtypes. In contrast, both ET-1 and sarafotoxin S6c, given as intravenous injections in conscious monkeys, produced transient, equipotent, and dose-related increases in blood pressure. The highest dose of sarafotoxin S6c (1 nmol kg-', i.v.) also caused a marked secondary depressor response (-80± 6 mmHg) that lasted approximately 10 min. The pressor responses suggest that the vasoconstrictor ETB-like receptors are present in cynomolgus monkeys. 4 The data suggest the presence of two distinct vasoconstrictor ET receptor subtypes on smooth muscle cells. The ETA receptors are primarily located on the high pressure side of the circulation. The vasoconstrictor ETB-like receptors appear to be concentrated on the low pressure side.

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“…Since BQ-123 and BE-18257B are spe* cific for the ET-A receptor, it seems improbable, therefore, that they mimick this part of the peptide. Indeed, several groups of workers [29][30][31][32] have now provided evidence to show that it is the tertiary structure of ET (in particular, the loop dictated by the two disulphide bridges) that represents the most critical factor in its recognition at the ET-A receptor. Specifically, it is noted that the disulphide-reduced ET [29], fully Cysprotected ET [30] and [Ala ~, Ala a, Ala j J, Ala Is] ET [31]~ as well as the ET derivative formed by cleaving at Lys 9 with lysyl endopeptidase [29], all have greatly reduced potency by comparison with native ET-1.…”

Section: Discussion • and Conclusionmentioning

confidence: 99%

Molecular modelling of the structures of endothelin antagonists Identification of a possible structural determinant for ET‐A receptor binding

Satoh

Barlow

1992

FEBS Letters

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Computer-aided molecular modelling of the endothclin (ET-A) receptor antagonists, BQ-123 and BE-18257B. shows that they have very similar 3D structures. Parts of their 3D structures are also shown to match closely with that reported for residues 6-8 in endothelind. On the basis of these similarities (and with supporting evidence from literature data on endothelin structure-activity relationships) a structural determinant is proposed for ET-A receptor binding, and novel designs of peptide are suggested for providing more potent and selective ET-A receptor antagonists.

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[Ala1,3,11,15]endothelin-1 analogs with ETB agonistic activity

Cited by 159 publications

References 18 publications

Differential localization of endothelin ET_a and ET_B binding sites in human placenta

Differential localization of endothelin ET_a and ET_B binding sites in human placenta

Evidence for a differential location of vasoconstrictor endothelin receptors in the vasculature

Molecular modelling of the structures of endothelin antagonists Identification of a possible structural determinant for ET‐A receptor binding

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[Ala1,3,11,15]endothelin-1 analogs with ETB agonistic activity

Cited by 159 publications

References 18 publications

Differential localization of endothelin ETa and ETB binding sites in human placenta

Differential localization of endothelin ETa and ETB binding sites in human placenta

Evidence for a differential location of vasoconstrictor endothelin receptors in the vasculature

Molecular modelling of the structures of endothelin antagonists Identification of a possible structural determinant for ET‐A receptor binding

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Differential localization of endothelin ET_a and ET_B binding sites in human placenta

Differential localization of endothelin ET_a and ET_B binding sites in human placenta