Receptor kinetics differ for endothelin-1 and endothelin-2 binding to Swiss 3T3 fibroblasts

Devesly, Pierre; Phillips, Penny E.; Johns, Anthony; Rubanyi, Gabor M.; Parker-Botelho, Lynne H.

doi:10.1016/s0006-291x(05)80182-2

Cited by 25 publications

(9 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…E3, however, was approximately 4 orders of magnitude less active than El. These data are in agreement with studies of the relative affinities of the various endothelins for fibroblast receptors [40,41].…”

Section: Endothelin 1 Is a Type B Promoter [21]supporting

confidence: 90%

“…The biologically active forms are quite small (21 amino acids) and have effects on both vascular and non-vascular tissues (reviews; [37,38]). E1 and E2 bind to high affinity receptors on both murine and human fibroblast cell surfaces [39,40], rapidly increasing the intracellular free Ca ++ concentration [39,41], stimulating phospholipase C [39,42] and protein kinase C activities [39,42] in a dose-dependent fashion. The binding of E3 to fibroblasts is negligible [41].…”

Section: Identification Of Endothelin 1 As An Endothelial Cell-secretmentioning

confidence: 99%

See 1 more Smart Citation

Extracellular matrix contraction by fibroblasts: Peptide promoters and second messengers

Guidry

1992

Cancer Metast Rev

View full text Add to dashboard Cite

Cells contracting connective tissue matrices generate tractional forces in tissues. Studies of fibroblast contraction, using collagen gels in an in vitro model, demonstrate that it involves the actin cytoskeleton, specific extracellular matrix receptors and requires stimulation by exogenous promoters. Fibroblast contraction is stimulated by factors released by platelets and potentially secreted within the contracting tissue. Endothelial cells secrete a potent promoter of fibroblast contraction which has been identified as endothelin 1. The pathway through which fibroblast contraction is stimulated appears to require activation of protein kinase C. Tumor cells can also secrete endothelin. These mechanisms may be relevant to tumor progression.

show abstract

Section: Endothelin 1 Is a Type B Promoter [21]supporting

confidence: 90%

Section: Identification Of Endothelin 1 As An Endothelial Cell-secretmentioning

confidence: 99%

Extracellular matrix contraction by fibroblasts: Peptide promoters and second messengers

Guidry

1992

Cancer Metast Rev

View full text Add to dashboard Cite

show abstract

“…Further studies with more potent ET A receptor agonists such as ET‐2 may prove beneficial, although presently there is a paucity of published studies describing the functional and radioligand binding characteristics of this ET isopeptide in the same cell or tissue type. Nevertheless, the binding of ET‐2 to Swiss 3T3 fibroblasts has been shown to be more readily reversible than the binding of ET‐1 (Devesly et al , 1990) and the contractions induced by ET‐1 and ET‐2 of rabbit iris sphincter muscle were similarly more resistant to inhibition by BQ‐123 than those induced by ET‐3 or StxS6b (Ishikawa et al , 1996). If this profile of responses to ET‐2 (i.e.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the contractile effects and binding kinetics of endothelin‐1 and sarafotoxin S6b in rat isolated renal artery

Devadason

Henry

1997

British J Pharmacology

View full text Add to dashboard Cite

1 To date, only two mammalian endothelin (ET) receptors, termed ET A and ET B , have been cloned, sequenced and characterized. However, several functional studies of isolated blood vessels suggest that ET-1-induced contractions may be mediated by multiple ET A receptors. In this study, the ET A receptors in renal arteries isolated from Wistar rats were characterized by isometric tension recording and radioligand binding techniques. 2 ET-1, sarafotoxin S6b (StxS6b) and ET-3 produced concentration-dependent contraction with similar response maxima in endothelium-denuded arteries, whereas the ET B receptor-selective agonist StxS6c was inactive. ET-1 and StxS6b were equipotent and 30 times more potent than ET-3. This agonist pro®le, together with the ®ndings that the ET A receptor-selective antagonists, BQ-123 and FR-139317 caused concentration-dependent, rightward shifts of the concentration-e ect curves to each agonist indicated that ET-1-induced contractions in rat renal artery were mediated via ET A receptors. 5 Thus, di erences in BQ-123 potency against ET-1 and StxS6b-induced contractions in rat renal arteries might be due to di erences in the kinetics of agonist binding, rather than due to the existence of atypical ET A receptors.

show abstract

“…Saturation curves were monophasic with the same association rate constants (K obs ) of 0.01 min −1 for [ 125 I]‐ET‐2 with [ 125 I]‐ET‐1 and similar slow dissociation rates (Roubert et al ., 1991). Intriguingly however, while [ 125 I]‐ET‐2 and [ 125 I]‐ET‐1 bound with the same affinity at ET A receptors in Swiss 3T3 fibroblasts, ET‐2 dissociated at a dramatically faster rate than ET‐1 did, which may be important in determining pharmacological responses to ET‐2 in vivo (Devesly et al ., 1990). It is not yet known whether kinetics of binding varies between cell types and can distinguish responses to the two isoforms in vivo .…”

Section: Unexplained Et‐2 Pharmacologymentioning

confidence: 99%

Endothelin‐2, the forgotten isoform: emerging role in the cardiovascular system, ovarian development, immunology and cancer

Ling

Maguire

Davenport

2012

British J Pharmacology

View full text Add to dashboard Cite

Endothelin-2 [ET-2; also known as vasoactive intestinal contractor (VIC), in rodents] differs from endothelin-1 (ET-1) by only two amino acids, and unlike the third isoform, endothelin-3 (ET-3), it has the same affinity as ET-1 for both ETA and ETB receptors. It is often assumed that ET-2 would mimic the actions of the more abundant ET-1 and current pharmacological interventions used to inhibit the ET system would also block the actions of ET-2. These assumptions have focused research on ET-1 with ET-2 studied in much less detail. Recent research suggests that our understanding of the ET family requires re-evaluation. Although ET-2 is very similar in structure as well as pharmacology to ET-1, and may co-exist in the same tissue compartments, there is converging evidence for an important and distinct ET-2 pathway. Specifically is has been demonstrated that ET-2 has a key role in ovarian physiology, with ET-2-mediated contraction proposed as a final signal facilitating ovulation. Furthermore, ET-2 may also have a pathophysiological role in heart failure, immunology and cancer. Comparison of ET-2 versus ET-1 mRNA expression suggests this may be accomplished at the level of gene expression but differences may also exist in peptide synthesis by enzymes such as endothelin converting enzymes (ECEs) and chymase, which may allow the two pathways to be distinguished pharmacologically and become separate drug targets. LINKED ARTICLESThis article is part of a themed section on Endothelin. To view the other articles in this section visit http://dx.doi. org/ 10.1111/bph.2013.168.issue-2 Abbreviations ECE-1, endothelin converting enzyme 1; ECE-2, endothelin converting enzyme 2; ELISA, enzyme-linked immunosorbent assay; HIFs, hypoxia-inducible factors; MEK1/2, mitogen-activated protein kinase kinase; MMP-2, matrix metallopeptidase 2; MMP-9, matrix metallopeptidase 9; NEP, neutral endopeptidase; PRKO, progesterone receptor knockout; PMA, phorbol 12-myristate 13 acetate; VIC, vasoactive intestinal contractor IntroductionThe existence of a peptidic endothelium-derived constricting factor was originally proposed in 1985 by Hickey et al. (Hickey et al., 1985) but was identified and named endothelin (ET) by colleagues in 1988 (Yanagisawa et al., 1988). The peptide was renamed ET-1 to reflect the subsequent discovery a year later of human genes encoding two further members of the family, ET-2 and ET-3 (Inoue et al., 1989). The ET peptides act by activating two G-protein couples receptors, ETA and ETB. (Davenport, 2002;Alexander et al., 2011) ET-3 is the only endogenous isoform that distinguishes between the two receptors, having the same affinity at ETB as ET-1 and ET-2 but, at physiological concentrations, has much lower or little affinity for ETA. The established dogma is that ET-2 has the same affinity for both ETA and ETB receptors as ET-1. It is often assumed that ET-2 would mimic the actions of the more abundant peptide, and current pharmacological interventions used to inhibit the ET system would also block the actions o...

show abstract

Receptor kinetics differ for endothelin-1 and endothelin-2 binding to Swiss 3T3 fibroblasts

Cited by 25 publications

References 19 publications

Extracellular matrix contraction by fibroblasts: Peptide promoters and second messengers

Extracellular matrix contraction by fibroblasts: Peptide promoters and second messengers

Comparison of the contractile effects and binding kinetics of endothelin‐1 and sarafotoxin S6b in rat isolated renal artery

Endothelin‐2, the forgotten isoform: emerging role in the cardiovascular system, ovarian development, immunology and cancer

Contact Info

Product

Resources

About