Sarafotoxin S6c: An agonist which distinguishes between endothelin receptor subtypes

Williams, David L.; Jones, Kathryn L.; Pettibone, Douglas J.; Lis, Edward; Clineschmidt, Bradley V.

doi:10.1016/0006-291x(91)91601-8

Cited by 365 publications

(180 citation statements)

References 10 publications

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“…An ET A receptor appeared to be involved in the contractile response to ET-I of the porcine coronary artery (Fukuroda et al 1992), but a non-ET A receptor, different from the ET n receptor, seemed to be involved as well (Harrison et al 1992). This contention was based on the finding that ET-3 recognized a sarafotoxin $6c (selective for the ET B receptor; Williams et al 1991) sensitive receptor, which was not recognized by ET-I, thus ruling out the ET R receptor. ET-1 has also been shown to cause potent contractions of human coronary artery segments (Chester et al 1989;Davenport et al 1989;Hems6n et al 1990), but until now the nature of the endothelin receptor in this particular tissue remains unknown.…”

Section: Endothefin Receptors In the Coronary Arterymentioning

confidence: 99%

Endothelin receptors in the human coronary artery, ventricle and atrium

Bax

Bruinvels

Suylen

et al. 1993

Naunyn-Schmiedeberg's Arch Pharmacol

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Summary.In the present experiments we investigated endothelin (ET) receptors in the human coronary artery, and in ventricular and atrial muscle using quantitative receptor autoradiography. These data indicate that both [125I]ET-1 and [125I] Sf6b-labeled ETA and ETB binding sites in human ventricular and atrial muscle. In the human coronary artery, both radioligands labeled ETA binding sites, but [125I] Sf6b also labeled a non-ET A, non-ETB binding site with relatively high affinity for both ET-1.

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Section: Endothefin Receptors In the Coronary Arterymentioning

confidence: 99%

Endothelin receptors in the human coronary artery, ventricle and atrium

Bax

Bruinvels

Suylen

et al. 1993

Naunyn-Schmiedeberg's Arch Pharmacol

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“…receptor (Williams et al, 1991), the cyclic peptide BQ123 (D-Asp-L-Pro-D-Val-L-Leu-D-Trp) is a highly selective ETA receptor antagonist (Ihara et al, 1992) and IRL1038 ([Cys"l-Cys']-endothelin-1(11-21)) is an ETB-selective antagonist (Urade et al, 1992;Karaki et al, 1993). By use of these agonists and antagonists it has been demonstrated in arteries from several species that the contractile response to endothelin-l is mediated via ETA receptors (Moreland et al, 1992;Sumner et al, 1992;Cardell et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Endothelin receptors mediating functional responses in human small arteries and veins

Riezebos

Watts

Vallance

1994

British J Pharmacology

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1 In the present study, responses of human omental small arteries and veins to endothelin-1 and endothelin-3 were characterized by use of the ETB receptor selective agonist, sarafotoxin S6c, the ETA receptor antagonist, BQ123, the ETB receptor antagonist, IRL1038, the NO-synthase inhibitor NGmonomethyl-L-arginine (L-NMMA, 300ELM) and indomethacin (10I1M).2 Small arteries (internal diameter 413 ± 22 Am) and parallel running veins (646 ± 35 Am) were mounted in a myograph under a normalized tension equivalent to 90% of a transmural pressure of 100 mmHg and 19 mmHg in vivo, respectively. 3 In small arteries and veins, endothelin-1 caused a concentration-dependent increase in wall tension (E.. = 3.90 ± 0.56 mN mm-' and 1.90 m ± 0.32 mN mm-' respectively, P < 0.05) and was equipotent (arteries: pD2 = 8.91 ± 0.11; veins: pD2 = 8.63 ± 0.08, NS). In endothelium intact arteries, L-NMMA significantly enhanced the sensitivity to endothelin-1 (pD2 control: 8.92 ± 0.16; pD2 L-NMMA: 9.37 ± 0.11; P<0.05). L-NMMA did not affect the sensitivity of veins to endothelin-1. Indomethacin was without effect in arteries and veins. In veins, endothelin-3 was about a hundred times less potent than endothelin-l and showed a biphasic response curve. Small arteries did not contract to endothelin-3. Neither small arteries nor veins contracted to sarafotoxin S6c. Furthermore, no relaxation to endothelin-1 or sarafotoxin S6c was seen in any precontracted vessels. 4 BQ123 (0.03-3 3LM) produced a concentration-dependent rightward parallel displacement of the endothelin-l concentration-response curve in small arteries and veins yielding pA2 values of 7.09 and 7.48 respectively. The slope of the Schild plot in arteries and veins was 1.26 ± 0.24 (NS from unity) and 0.61 ± 0.13 (P <0.05 compared to unity) respectively. IRL1038 (3 JLM) did not affect the potency of endothelin-1 in arteries and veins. In veins, the low sensitivity component (pD2 = 7.16 ± 0.08) of the biphasic response curve to endothelin-3 was completely blocked by BQ123 (31JM), whereas the high sensitivity component (pD2 = 8.66 ± 0.08) was resistant to BQ123 (3 JiM) and IRL1038 (3 JAM).5 These results indicate that contractions of human small vessels to endothelin-l are predominantly mediated by ETA receptors and that nitric oxide modulates the response to endothelin-l in small arteries but not in veins. The different antagonistic potency of BQ123 against endothelin-l and the differential endothelin-1/endothelin-3 potency ratios in arteries and veins provide evidence for the hypothesis that ETA receptors in human small arteries are different from ETA receptors in human small veins. There is no evidence of contractions mediated by 'classical' ETB receptors in these vessels, but small veins appear to contain a functional non ETA/non ETB receptor with a high affinity for endothelin-3.

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“…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%

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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Sarafotoxin S6c: An agonist which distinguishes between endothelin receptor subtypes

Cited by 365 publications

References 10 publications

Endothelin receptors in the human coronary artery, ventricle and atrium

Endothelin receptors in the human coronary artery, ventricle and atrium

Endothelin receptors mediating functional responses in human small arteries and veins

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

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Sarafotoxin S6c: An agonist which distinguishes between endothelin receptor subtypes

Cited by 365 publications

References 10 publications

Endothelin receptors in the human coronary artery, ventricle and atrium

Endothelin receptors in the human coronary artery, ventricle and atrium

Endothelin receptors mediating functional responses in human small arteries and veins

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

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Product

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