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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Different pharmacological profiles of big-endothelin-3 and big-endothelin-1 in vivo and in vitro.

1. Human big-endothelin-1 (big-ET-1) and endothelin-1 (ET-1) are equipotent as pressor agents and produce a significant change in mean arterial blood pressure (MAP) in anaesthetized guinea-pigs (2 nmol kg-1: peak delta MAP: 23 +/- 6 mmHg and 26 +/- 5 mmHg, respectively). 2. Unlike big-ET-1, big-endothelin-3 (big-ET-3) (10 and 20 nmol kg-1) induces no pressor responses whereas endothelin-3 (ET-3) at 2 nmol kg-1 induces a significant increase of blood pressure in anaesthetized guinea-pigs (peak delta MAP: 27 +/- 5 mmHg) with a shorter duration than ET-1 and big-ET-1. 3. Big-ET-1 at concentrations 40 times higher than those required for ET-1 (2.5 nM) releases prostacyclin (PGI2) (maximal release: 2.7 +/- 0.8 ng ml-1; 2.9 +/- 0.9 ng ml-1, respectively) and thromboxane B2 (TxB2) (maximal release: 6.7 +/- 1.3 ng ml-1; 6.8 +/- 1.1 ng ml-1, respectively) from guinea-pig perfused lungs. ET-3 (2.5 nM) is also a potent releaser of PGI2 and TxB2 from the guinea-pig lungs (maximal release: PGI2: 2.4 +/- 1.0 ng ml-1; TxB2: 3.8 +/- 0.6 ng ml-1). Conversely, big-ET-3 (100 nM) does not increase basal release of eicosanoids. 4. Phosphoramidon (50 microM), a metalloprotease inhibitor, markedly reduced the eicosanoid releasing properties of big-ET-1 (n = 4, P less than 0.01) in guinea-pig perfused lungs without affecting the release stimulated by ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


  1. Different pharmacological profiles of big-endothelin-3 and big-endothelin-1 in vivo and in vitro. D'Orléans-Juste, P., Télémaque, S., Claing, A. Br. J. Pharmacol. (1991) [Pubmed]
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