Synthesis and degradation of endothelin-1.
The endothelin-converting enzyme (ECE) is the main enzyme responsible for the genesis of the potent pressor peptide endothelin-1 (ET-1). It is suggested that the ECE is pivotal in the genesis of ET-1, considering that the knockout of both genes generates the same lethal developments during the embryonic stage. Several isoforms of the ECE have been disclosed, namely ECE-1, ECE-2, and ECE-3. Within each of the first two groups, several sub-isoforms derived through splicing of single genes have also been identified. In this review, the characteristics of each sub-isoform for ECE-1 and 2 will be discussed. It is important to mention that the ECE is, however, not the sole enzyme involved in the genesis of endothelins. Indeed, other moieties, such as chymase and matrix metalloproteinase II, have been suggested to be involved in the production of ET intermediates, such as ET-1 (1-31) and ET-1 (1-32), respectively. Other enzymes, such as the neutral endopeptidase 24-11, is curiously not only involved in the degradation and inactivation of ET-1, but is also responsible for the final production of the peptide via the hydrolysis of ET-1 (1-31). In this review, we will attempt to summarize, through the above-mentioned characteristics, the current wisdom on the role of these different enzymes in the genesis and termination of effect of the most potent pressor peptide reported to date.
D'Orléans-Juste
P
P
Department of Pharmacology, Medical School, Institut de pharmacologie de Sherbrooke, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada. pedro.dorleans-juste@USherbrooke.ca
Plante
M
M
Honoré
J C
JC
Carrier
E
E
Labonté
J
J
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000378:metabolism; D000072396:Endothelin-Converting Enzymes; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008666:Metalloendopeptidases; D008969:Molecular Sequence Data
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; C000606924:ECE2 protein, human; D000072396:Endothelin-Converting Enzymes