A potent and specific agonist, Suc-[Glu9,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptor

Takai, Makoto; Umemura, Ichiro; Yamasaki, Kazuhiko; Watakabe, Tadashi; Fujitani, Yasushi; Oda, Kyoko; Urade, Yoshihiro; Inui, Takashi; Yamamura, Takehira; Okada, Toshikazu

doi:10.1016/0006-291x(92)90683-c

Cited by 215 publications

(77 citation statements)

References 20 publications

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“…Related tissue sections were incubated in vitro with 1 nM [125I]q endothelin-1 (ET-1) in the incubation buffer at 4°C for 48 h, as described (Niwa et al, 1992). In brief, after preincubation in incubation buffer (50 mM Tris-HCl buffer (pH 7.4) containing: NaCl 100 mM, EDTA-2Na 10 mM, phosphoramidon 10 pM, bacitracin 1 mg ml-', leupeptin 4 pg ml-', chymostatin 2 pg ml-' and 0.3% bovine serum albumin (protease-free)) at 23°C for 10 min, tissue sections were incubated in 2 ml of incubation buffer containing ['"I]-ET-1 at 4°C for 48 h. Consecutive tissue sections were labelled to characterize ['251]-ET-1 binding in the presence of 1 pM unlabelled ET-1 (nonspecific binding), 10 pM BQ 123, a highly selective antagonist for the endothelin ETA receptor (Ihara et al, 1991), 10 pM BQ 788, a highly selective antagonist for the endothelin ETB receptor (Ishikawa et al, 1994) or 10 pM IRL 1620, a highly selective agonist for the endothelin ETB receptor (Takai et al, 1992).…”

Section: Receptor Autoradiographymentioning

confidence: 99%

Localization of endothelin ET_B receptors on the myenteric plexus of guinea‐pig ileum and the receptor‐mediated release of acetylcholine

Yoshimura

S-Yamashita

Kan

et al. 1996

British J Pharmacology

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Section: Receptor Autoradiographymentioning

confidence: 99%

Localization of endothelin ET_B receptors on the myenteric plexus of guinea‐pig ileum and the receptor‐mediated release of acetylcholine

Yoshimura

S-Yamashita

Kan

et al. 1996

British J Pharmacology

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“…ET-1 (human and porcine type) and big ET-1 (human type) (both from Peptide Institute, Osaka, Japan) were dissolved under aseptic conditions in sterile water containing 0'05% human serum albumin (ET-1, 0-2 mg ml-; big ET-1, 0 4 mg ml-'). Aliquots of these stock solutions were stored at -20°C and, on the day of the experiment, were diluted with (Takai et al 1992), was dissolved in 0-01 N NaOH (0-2 mg ml-') and aliquots (stored at -20°C) (Wang & Coceani, 1992 (Wang, Mercer-Connolly, Lines, Toyoda & Coceani, 1994). These segments of arteries and veins contribute to normal pulmonary vascular resistance in the fetus and are involved in the transitional adjustments at birth (Wang & Coceani, 1992.…”

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confidence: 99%

Involvement of endothelin‐1 in hypoxic pulmonary vasoconstriction in the lamb.

Wang

Coe

Toyoda

et al. 1995

The Journal of Physiology

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1. Using isolated pulmonary resistance vessels from mature fetal lamb and chronically instrumented lambs (8-17 days old), we have examined whether hypoxic pulmonary vasoconstriction is sustained by activation of a constrictor mechanism or suppression of a dilator mechanism. 2. Hypoxia contracted both arteries and veins in vitro, and the contraction was greater with the former. After removing the endothelium, arteries responded faster to hypoxia, but the magnitude of the response remained unchanged. 3. Hypoxic arteries, unlike normally oxygenated arteries, did not contract with either indomethacin (2-8 uM) or NT-nitro-L-arginine methyl ester (L-NAME, 100 UM). The same vessels relaxed with sodium nitroprusside (SNP, 0.001-10 /1M) but not with bradykinin (0-1-100 nM).4. Endothelin-1 (ET-1, 0-01-10 nM) contracted isolated arteries and veins under normoxic and hypoxic conditions. In both vessels, the contraction was fast in onset and subsidence, and was inhibited by the ETA receptor antagonist BQ123 (1 /SM). The ET-1 precursor, big ET-1 (100 nM), also contracted arteries and veins, but compared with ET-1 its action was slower in development. Big ET-1 contraction, unlike ET-1 contraction, was curtailed by the inhibitor of the ET-1 -converting enzyme, phosphoramidon (50 ,UM). 5. ET-1 (01-10 nM) had no effect on isolated arteries precontracted with a thromboxane A2 (TXA2) analogue (ONO-11113) and treated with BQ123 (10 ,UM). Under the same conditions, ET-1 relaxed the veins. Accordingly, in the absence of BQ123 treatment, the selective ETB receptor agonist IRL-1620 (0-1-100 nM) relaxed the contracted veins but not the arteries.6. BQ123 (10/M) inhibited the constriction of isolated arteries and veins to hypoxia.Likewise, in the conscious lamb a bolus of BQ123 (0 4 mg kg-', injected into the pulmonary artery) curtailed the rise in pulmonary vascular resistance (Rpa) brought about by alveolar hypoxia without changing significantly systemic vascular resistance (Ra0). Under normoxia, Rpa was insignificantly affected by BQ123.7. The results indicate that pulmonary resistance arteries are more susceptible to hypoxia than the veins, and that hypoxic vasoconstriction does not require an intact endothelium to occur. Hypoxic tone is ascribed primarily to intramural generation of ET-1, while removal of the tonic action of a relaxant may only have an accessory role in the response.It is well known that the pulmonary vasculature constricts optimal matching of blood flow to alveolar hypoxia when ambient oxygen tension falls below the normal range (Fishman, 1990). In its extreme manifestation, hypoxic (reviewed by Fishman, 1990). This response is evident in vasoconstriction may lead to pulmonary hypertension

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“…IRL 1620, a selective ETB receptor agonist [19], showed a contractile response similar to that induced by the ETs. The ETA receptor antagonist FR139317 did not affect the ET-1-induced contraction, whereas the combined ET-receptor antagonist PD 145065 (1 µM) shifted the IRL 1620-induced concentrationresponse curve to the right in a competitive manner, suggesting that the contraction of human small bronchi is mediated mainly by ETB receptors.…”

Section: Discussionmentioning

confidence: 88%

“…The aim of the present study was to characterize the ET subreceptors in human small airways by the use of different pharmacological tools; IRL 1620, a selective ETB receptor agonist [19], FR139317, a selective ETA receptor antagonist [18,20], and PD 145065, a newly developed combined ETA and ETB receptor antagonist [21].…”

mentioning

confidence: 99%

Contractile endothelin-B (ETB) receptors in human small bronchi

Adner

Cardell²,

Sjöberg

et al. 1996

Eur Respir J

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C Co on nt tr ra ac ct ti il le e e en nd do ot th he el li in n--B B ( (E ETTBIn the present paper, improved methodology was used which enables in vitro studies of small human bronchi down to a diameter of 0.5-1.0 mm. Using the new methodology we have tried to further characterize this receptor.Small bronchi from the distal parts of the bronchial tree were obtained from pulmonary tissue removed from 15 patients with lung cancer. They were dissected and cut into ring segments, in which isometric tension was recorded.ET-1, ET-2 and ET-3 elicited strong concentration-dependent contractions of the human small bronchus. Basically, the three peptides were equipotent with about the same maximal response. Upon reapplication, they all showed the same tachyphylaxis pattern, reaching half the initial contraction. Comparative analysis of IRL 1620, a selective ETB receptor agonist, revealed that the effect of the ETB agonist was, in all respects, similar to the responses induced by the ETs. PD 145065, a combined ETA/ETB receptor antagonist competitively inhibited the contractions induced by IRL 1620, whereas FR139317, a selective ETA receptor antagonist, was without effect.In conclusion, the present study shows that accurate measurements can be made in vitro on small human bronchi and all present data are in favour of an ETB receptor mediating endothelin-induced contraction of human bronchi smaller than 1.0 mm.

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A potent and specific agonist, Suc-[Glu9,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptor

Cited by 215 publications

References 20 publications

Localization of endothelin ET_B receptors on the myenteric plexus of guinea‐pig ileum and the receptor‐mediated release of acetylcholine

Localization of endothelin ET_B receptors on the myenteric plexus of guinea‐pig ileum and the receptor‐mediated release of acetylcholine

Involvement of endothelin‐1 in hypoxic pulmonary vasoconstriction in the lamb.

Contractile endothelin-B (ETB) receptors in human small bronchi

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A potent and specific agonist, Suc-[Glu9,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptor

Cited by 215 publications

References 20 publications

Localization of endothelin ETB receptors on the myenteric plexus of guinea‐pig ileum and the receptor‐mediated release of acetylcholine

Localization of endothelin ETB receptors on the myenteric plexus of guinea‐pig ileum and the receptor‐mediated release of acetylcholine

Involvement of endothelin‐1 in hypoxic pulmonary vasoconstriction in the lamb.

Contractile endothelin-B (ETB) receptors in human small bronchi

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Localization of endothelin ET_B receptors on the myenteric plexus of guinea‐pig ileum and the receptor‐mediated release of acetylcholine

Localization of endothelin ET_B receptors on the myenteric plexus of guinea‐pig ileum and the receptor‐mediated release of acetylcholine