Disease relevance of Edn2

• Cobalt chloride induces neurite outgrowth in rat pheochromocytoma PC-12 cells through regulation of endothelin-2/vasoactive intestinal contractor [1].
• We isolated two proteins, ET-1 and ET-2, from the sporangial extracts of Clostridium perfringens type A. Both proteins had some properties in common with the well-known C. perfringens enterotoxin [2].
• In isolated stimulated rat atria, superfusion with veratrine caused a marked contracture (VIC) which was absent in calcium-free medium and which was inhibited by tetrodotoxin (IC50VIC of 1.38 microM) [3].
• ET-1, ET-2, ET-3 and sarafotoxin S6b (STX) induced rhythmic contractions superimposed on an increased muscle tone [4].
• ET-2 promoter, which is the 5'-flanking region of preproET-2 gene (5'ET-2), showed a marked increase in luciferase activity during acute hypoxia [5].

High impact information on Edn2

• We found that the gene coding for endothelin-2 (ET2), also known as vasoctive intestine peptide, cosegregated strongly with systolic blood pressure in a F2 population [F2(S x LEW)] derived from a cross of the Dahl salt-sensitive (S) rat and the Lewis (LEW/NCrlBR) (LEW) rat [6].
• The ET2 locus was assigned to rat chromosome 5 [6].
• We conclude that, in the rat, one new blood pressure QTL is located on chromosome 5 marked by the ET2 locus and another new QTL is located on chromosome 17 near the HITH locus [6].
• Endothelin (ET)-3 dose-dependently stimulated cGMP accumulation in glomerulus, which was higher than that of ET-1 or ET-2 [7].
• ET2 was expressed at high level in both large and small intestine and at low level in stomach, muscle, and heart, but ET2 mRNA could not be detected elsewhere [8].

Chemical compound and disease context of Edn2

• Diltiazem, verapamil and nifedipine only reduced veratrine-induced contracture at concentrations much higher than those producing a negative inotropic effect, giving them negative NIE/VIC ratios of 0.31, 0.08 and 0.08 respectively [3].
• ET-2 (50 ng/kg, iv) and ET-3 (50 ng/kg, iv) had similar antagonistic effect on clonidine induced hypotension and bradycardia [9].
• The response to VIC was suppressed either by the external application to BAPTA/AM (10 microM) or by pertussis toxin 0.5 microgram/ml) [10].

Biological context of Edn2

• When the cells were treated with 500 microM CoCl2 for 24 hr, however, ET-2/VIC gene expression disappeared, IL-6 gene expression was downregulated, and necrosis was subsequently induced in the PC-12 cells [1].
• ET-1, ET-2 and SRT6b produced a decrease in blood pressure (51%, 47% and 41%, respectively) along with a decrease in cardiac output (58%, 60% and 45%, respectively) and stroke volume [11].
• The systemic haemodynamics and regional blood circulation in urethane anaesthetized rats following intracerebroventricular (i.c.v.) administration of ET-1, ET-2, SRT6b, ET-3 and SRT6c (10, 30 and 90 ng) were determined by a radioactive microsphere technique [11].
• By screening a cDNA library derived from the A10 rat vascular smooth muscle cell line for functional expression in COS cells, we have isolated a high-affinity receptor for endothelin 1 (Kd = 476 pM) and endothelin 2 [12].
• In addition to the increase in cytosolic free [Ca2+] ([Ca2+]i) previously described for ET-1, we also observed that ET-2, ET-3, and sarafotoxin S6b generate similar [Ca2+]i waveforms but with dissimilar potencies and kinetics [13].

Anatomical context of Edn2

• Hence, we presume that ETs are synthesized in and secreted from stromal cells in the rat gastrointestinal tract, that their main isotypes are not only ET-2 but also ET-3, and that ETs may act in an autocrine/paracrine fashion [14].
• ET-1, ET-2 and SRT6b also produced a significant reduction in blood flow to the brain, kidneys, heart, portal, mesentery and pancreas, gastrointestinal tract (GIT) and musculoskeletal system [11].
• The endothelins represent a family of three (ET-1, ET-2, and ET-3) isopeptides that are derived from vascular endothelial cells and function as potent vasoconstrictors [15].
• ET-R1 was also expressed in cultured rat glomerular mesangial cells based on findings of a subset of receptors with an apparent molecular mass of 73 kDa that bound 125I-ET-1 displacable by endothelin-1 and endothelin-2 but not by endothelin-3 [16].
• In rings of rat portal vein, endothelin-1, endothelin-2, and endothelin-3 caused graded slow contractions and potentiated spontaneous contractions [17].

Associations of Edn2 with chemical compounds

• In contrast, bosentan delayed the rate of onset, and reduced the duration, of the mesenteric vasoconstrictor actions of ET-2 and ET-3 [18].
• Intracerebroventricular injection of 6, 12, and 20 ng ET-2 resulted in a significant, dose-related inhibition of water drinking in response to subsequent injection of 100 pmol angiotensin II (ANG II) [19].
• The fibres contracted in response to treatment with KCl (80 mM), ACh (100 microM), endothelin-1 (10 nM), endothelin-2 (10 nM), and prostaglandin F2alpha (100 microM) [20].
• PRL release inhibition by VIC was not mediated via the D2-dopamine receptor and was not prevented by calcium channel blockade with 100 nM nifedipine [21].
• ET-2 was the more anionic protein since it eluted more slowly from the anion exchange column and migrated faster toward the anode in polyacrylamide disk gel electrophoresis (pH 8.5, native gels) [2].

Analytical, diagnostic and therapeutic context of Edn2

• RT-PCR analysis, morphological observations, and immunostaining revealed that CoCl2, a hypoxic mimetic agent, at 200 microM increased expression of the ET-2/VIC gene, decreased expression of the ET-1 gene, and induced neurite outgrowth in PC-12 rat pheochromocytoma cells [1].
• Both ET-1 and ET-2 showed lines of identity in agar gel double immunodiffusion against anti-enterotoxin antiserum [2].
• 1. The response of the cutaneous microvasculature to intradermal injection of the endothelins (ET-1, ET-2 and ET-3) and the modulatory effect of endogenously produced nitric oxide (NO) have been determined in the rat [22].
• The influence of endothelin on vascular and myocardial reperfusion damage was studied with exogenous endothelin-2 [23].
• After 1 h of low-flow ischaemia, endothelin-2 increased the coronary perfusion pressure to a similar extent as in non-ischaemic hearts, but with a 30-times higher potency [23].

References