Big Endothelin-1 (1-38) (human) (trifluoroacetate salt)

Big endothelin-1 (BET-1) (1-38) is a peptide precursor of endothelin-1 (Item No. 24127) produced by vascular smooth muscle and endothelium.1 BET-1 is converted to endothelin-1 by endothelin-converting enzyme (ECE) and to endothelin-1 (1-31) by chymase.2 It is also converted to endothelin-1 (1-32) by matrix metalloproteinase-2 (MMP-2).1 BET-1 (50 pmol) induces vasoconstriction in isolated rat mesenteric arteries, an effect that is blocked by the MMP-2 antagonist TIMP-2. In vivo, BET-1 (0.1-10 nmol/kg, i.v.) dose-dependently increases blood pressure and bradycardia and leads to renal and hindquarter vasoconstriction in rats as well as abdominal constriction in mice (ED50 = 0.043 mg/kg), effects that are reversed or prevented by the ECE inhibitor phosphoramidon (Item No. 15113).3,4 It also induces mesenteric vasoconstriction in rats.3 Unlike endothelin-1, BET-1 (100 pmol/kg, i.v.) increases water and sodium excretion in rats independent of the endothelin A receptor.5WARNING This product is not for human or veterinary use.

[1] C FERNANDEZ-PATRON  S T D  M W Radomski. Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a novel vasoconstrictor.[J]. Circulation research, 1999, 85 10: 906-911. DOI: 10.1161/01.res.85.10.906
[2] P D’ORLÉANS-JUSTE. Synthesis and degradation of endothelin-1.[J]. Canadian journal of physiology and pharmacology, 2003, 81 6: 503-510. DOI: 10.1139/y03-032
[3] SHEILA M. GARDINER. The effects of phosphoramidon on the regional haemodynamic responses to human proendothelin [1–38] in conscious rats[J]. British Journal of Pharmacology, 1991, 103 4: 2009-2015. DOI: 10.1111/j.1476-5381.1991.tb12368.x
[4] ROBERT B. RAFFA  Henry I J. Endothelin-1, -2 and -3 directly and big-endothelin-1 indirectly elicit an abdominal constriction response in mice[J]. Life sciences, 1991, 48 17: Pages PL85-PL90. DOI: 10.1016/0024-3205(91)90130-4
[5] DAVID M. POLLOCK  Terry J O. ETA receptor-mediated responses to endothelin-1 and big endothelin-1 in the rat kidney[J]. British Journal of Pharmacology, 1994, 111 3: 729-732. DOI: 10.1111/j.1476-5381.1994.tb14798.x