Disease relevance of Edn2

• Primary structure of cat preproendothelin-2 and cat renal mRNA expression of preproendothelin-1 and preproendothelin-2 in naturally occurring renal failure [1].
• Transfection of ACHN adenocarcinoma cells with the cDNA resulted in the production of VIC peptide [2].
• The endothelin-2/vasoactive intestinal contractor gene: expression and promoter activity in PC12 rat pheochromocytoma cells [3].

High impact information on Edn2

• The significant residual ET-1/ET-2 in the ECE-1(-/-); ECE-2(-/-) embryos indicates that proteases distinct from ECE-1 and ECE-2 can carry out ET-1 activation in vivo [4].
• Taken together these observations suggest that VIC may have contractile properties, which can account for a controlled tonus, actively correlated with the cyclically changing forces acting on valves during diastole and systole [5].
• Furthermore, bombesin, vasopressin, and VIC markedly increased the rate of phosphorylation of Raytide, a broad specificity tyrosine kinase peptide substrate, by decreasing (8 +/- 1.3-fold) the apparent Km of the kinase for the substrate [6].
• Neuropeptides increased the labeling of p115 within seconds and with great potency; half-maximum concentrations were 0.1, 0.2 and 0.3 nM for bombesin, vasopressin, and VIC, respectively [6].
• We also identified cGMP-dependent protein kinase II, a previously reported PGR-regulated gene, as a downstream target of ET-2 during ovulation [7].

Biological context of Edn2

• A high level of VIC gene expression was observed in ovary and uterus [8].
• Gene expression of vasoactive intestinal contractor/endothelin-2 in ovary, uterus and embryo: comprehensive gene expression profiles of the endothelin ligand-receptor system revealed by semi-quantitative reverse transcription-polymerase chain reaction analysis in adult mouse tissues and during late embryonic development [8].
• The PPVIC gene contains five exons that span 6 kb and shows a duplication on exons 2 and 3, coding for the VIC and VIC-like peptides respectively [9].
• Homology analysis showed that the similarity of the cat PPET-2 amino acid sequence with those from human, mouse, rat, rabbit, dog, ferret, cow, and horse was 73.0%, 68.6%, 69.1%, 76.4%, 81.2%, 83.1%, 76.3%, and 79.2%, respectively [1].
• Analysis of PPET-1 and PPET-2 mRNA in cat by reverse transcription polymerase chain reaction showed upregulated expression of both genes in kidneys affected by renal failure [1].

Anatomical context of Edn2

• Thus, VIC may have some physiological role in adult ovary and uterus as well as intestine [8].
• VIC/ET-2 gene expression was observed at high levels in the pituitary gland and medulla oblongata in both the mouse and rat [10].
• Vasoactive intestinal contractor/endothelin-2 gene expression in the murine central nervous system [10].
• Increased gene expression of endothelin-1 and vasoactive intestinal contractor/endothelin-2 in the mammary gland of lactating mice [11].
• Cold injury to the mouse cerebral cortex caused a significant decrease in VIC/ET-2 gene expression in this structure, whilst expression of the ET-1 gene was increased [10].

Associations of Edn2 with chemical compounds

• The endothelin-related peptide, vasoactive intestinal contractor, also elicited a rapid and concentration-dependent tyrosine/serine phosphorylation of a similar set of substrates [12].
• Lowering the extracellular concentration of calcium by the addition of 1 mmol/liter EGTA did not inhibit the effect of ET-2 on cAMP induced renin secretion and renin gene expression [13].
• The inhibitory effects of [D-Arg1,D-Phe5,D-Trp7,9,Leu 11] substance P on Ca2+ mobilization and DNA synthesis were reversed by increasing the concentration of VIC [14].
• In this study, biphasic Ca(2+) signals elicited with endothelin (ET)-1, ET-2, ET-3, beta-ET, S6a1, and S6b (ET/S6) were measured by microspectrofluorimetric methods in cell suspensions loaded with Fura-2 acetoxymethylester (Fura-2 AM) [15].

Physical interactions of Edn2

• This is the first time that a peptide structurally unrelated to ET1 or VIC is shown to block the binding and mitogenic effects of peptides of the endothelin family [14].

Regulatory relationships of Edn2

• Inhibition of endothelin (ET)-1-and ET-2-induced vasoconstriction by anti-ET-1 monoclonal antibody [16].
• The adenylate cyclase activator forskolin (3 mumol/ liter) increased renin mRNA levels to 400% of the controls and this stimulation was dose-dependently attenuated by ET-2 to 250% of the control value [13].

Other interactions of Edn2

• The gene expression of VIC, relative to that of glyceraldehyde-3-phosphate dehydrogenase, was approximately 2.0%, 0.4%, and 2.3% in ovary, uterus, and intestine respectively, and was approximately 1.6 and 7 [8].
• The results also imply that ET-1, ET-2, ET 3 or big-ET-1[1-38] may be nociceptive under certain conditions [17].
• The effect of ET-2 was mimicked by the ETB-receptor agonist sarafotoxin S6c [13].
• A novel pathway involving progesterone receptor, endothelin-2, and endothelin receptor B controls ovulation in mice [7].

Analytical, diagnostic and therapeutic context of Edn2

• A novel peptide, vasoactive intestinal contractor, of a new (endothelin) peptide family. Molecular cloning, expression, and biological activity [18].
• Sequence analysis indicates that a biologically active mature VIC peptide is produced from a 175-residue precursor protein; preproVIC (PPVIC) [2].
• Rapid quantification of murine endothelin-1 and vasoactive intestinal contractor gene expression levels by a real-time PCR system [19].
• When injected intraperitoneally into mice, endothelins ET-1, ET-2, ET-3 and big-endothelin-1[1-38] (big-ET-1[1-38]) produced a dose-related, robust and easily quantified abdominal constriction response within 20 min [17].
• We produced a monoclonal antibody to endothelin (ET)-1, tested cross-reactivities with the related peptides by enzyme immunoassay, and investigated the effects of the antibody on ET-1- or ET-2-induced vasoconstriction of rat isolated thoracic aorta [16].

References