A novel 31-amino-acid-length endothelin, ET-1(1-31), can act as a biologically active peptide for vascular smooth muscle cells.
Human chymase produces a novel endothelin-1 with 31 amino-acid length ¿ET-1(1-31)¿, which is longer than conventional ET-1, ¿ET-1(1-21)¿. The aim of our study was to investigate the role of ET-1(1-31) on porcine coronary vascular smooth muscle cell (VSMC). Although the increase in [Ca(2+)](i) by ET-1(1-31) was 10 times weaker than that of ET-1(1-21), ET-1(1-31) showed equivalent potency in VSMC proliferation, c-fos/c-myc mRNA expression and cell cycle analysis with ET-1(1-21). ET-1(1-31) significantly induced expression of cyclin D1 but not those of cyclin D2 or D3. These effects were specifically inhibited by BQ485, an ET(A) receptor antagonist, although that of ET-1(1-21) was not specific to BQ485, suggesting different receptor specificity from ET-1(1-21). These results indicate that ET-1(1-31) also can involve a VSMC proliferation process such as atherosclerosis, although it has weaker vasoconstricting potency and different receptor subtypes on VSMC from those of ET-1(1-21).
Nagata
N
N
Department of Nutrition, School of Medicine, Tokushima, Kuramoto-Cho 3-18-15, 770-8503, Japan.
Niwa
Y
Y
Nakaya
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000031:analogs & derivatives; D016232:Endothelins / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D016259:Genes, myc; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D018919:Neovascularization, Physiologic; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine
D056741:Cyclin D; D016213:Cyclins; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D010446:Peptide Fragments; D012333:RNA, Messenger; C114932:endothelin-1 (1-31); D002118:Calcium