triclosan products kinase Since ET was discovered first and
Since ET-1 was discovered first and showed a wide variety of actions not only on the cardiovascular system but also on various other tissues, much information has accumulated on ET-1 compared with the two other peptides. The method for measurement of ET-1 levels in plasma or various tissues by means of radioimmunoassay (RIA) or enzyme immunoassay (EIA)  was established soon after the discovery of ET-1. RIA employs only one kind of antibody against ET-1, while EIA uses two kinds of antibodies, each recognizing the N-terminal and C-terminal portions of ET-1, respectively. At an early stage, the reported plasma concentrations of ET-1 in humans were fairly divergent, ranging from 0.2 to 18.5 pg/ml in healthy subjects. To avoid unnecessary confusion, the reason for the difference in the values of plasma ET-1 level was examined thoroughly and, as a result, it was generally agreed that the divergence originated mostly from differences in the specificity of the triclosan products kinase used and in the recovery rate during extraction of ET-1 from plasma or tissues. It is accepted now that the plasma concentration of ET-1 in healthy subjects is 1.0〜2.0 pg/ml , which is at least one order of magnitude lower than that of circulating human natriuretic peptides and several times less than that of AII. Plasma concentrations of ET-1 increase drastically in the case of various cardiovascular diseases .
ET-1 may be released in both luminal and abluminal directions from endothelial cells in vivo. Luminal released ET-1 may be diluted by the blood stream, and its circulating concentration (1.0〜2.0 pg/ml) is below the threshold concentration producing vasoconstriction. Although the exact concentration in the abluminal space (vascular smooth muscle surface) is not known, ET-1 is more likely to be a locally acting rather than a circulating hormone. When ET-1 production and secretion are increased drastically in certain place at pathophysiological conditions, severe local vasoconstriction might be anticipated.
When ET-1 is intravenously administered as a bolus, it disappears quite rapidly from the blood stream with a half-life of a few minutes. This rapid removal of ET-1 from the circulation results from uptake into various tissues, including the lung, kidney, spleen, and liver. The lung appears to be one of the most important tissues for uptake, since approximately 60% of ET-1 is removed after a single passage through the pulmonary circulation. In lung tissues, the ETB receptor is highly expressed and ET-1-ETB receptor complex may be taken up into cells through an internalization process and degraded by lysozomal enzymes, e.g., aspartic proteases. Neutral endopeptidase and lysozomal cathepsin G are also concerned with enzymatic degradation of ET-1. In spite of such a rapid disappearance from the circulation, the blood pressure-elevating effect of ET-1 continues for an extremely long period; stabilization of the ET-1-ETA receptor complex may contribute, but the exact reason for this phenomenon is unknown.
Biological actions within the cardiovascular system ET-1 causes extremely potent and long-lasting vasoconstriction in most mammalian species including humans, both in vivo and in vitro. The in vivo hemodynamic responses to intravenously injected ET-1 are complex, depending upon the vascular bed, and include both direct vasoconstriction and indirect endothelium-mediated vasodilatation, and reflex-mediated responses. In most arterial and some venous smooth muscle cells, ET-1 causes constrictor responses via stimulation of ETA receptors on the cell membrane. By contrast, ET-1 stimulates ETB receptors on endothelial cells and releases EDRF (endothelium-derived relaxing factor: nitric oxide), thereby producing vasodilatation. In cardiac muscle cells, ET-1 produces positive inotropic and chronotropic responses via stimulation of mostly ETA receptors. Both ETA and ETB receptors are coupled to various GTP-binding proteins (Gq, Gs, Gi, Go, etc.), suggesting that the downstream signal transduction may differ in various cells depending on the type of GTP-binding proteins coupled.