Novel 31-amino-acid-length endothelins cause constriction of vascular smooth muscle.
We have reported that human chymase specifically cleaves big endothelins (ETs) at the Try31-Gly32 bond, and produces novel trachea-constricting 31-amino-acid-length ETs, ETs(1-31). In this study, we investigated the effect of synthetic ETs(1-31) on the contractile activity toward porcine coronary arteries and rat aortae. Although ETs(1-31) exhibited less potent vasoconstrictile activity in these tissues than 21-amino-acid-length ETs(1-21), or a similar extent, ET-1(1-31) caused significantly slower-developing and longer-lasting contraction than ETs(1-21). The ETA receptor antagonist, BQ485, completely inhibited the activity of ET-1(1-31). The ETB receptor antagonist, BQ788, also inhibited the activity of ET-1(1-31) toward rat aortae more efficiently than that ET-1(1-21). Therefore, trachea-constricting peptides ETs(1-31) play roles as vasoconstrictors in a different manner from ETs(1-21).
Kishi
F
F
School of Medicine, University of Tokushima, Tokushima, 770, Japan.
Minami
K
K
Okishima
N
N
Murakami
M
M
Mori
S
S
Yano
M
M
Niwa
Y
Y
Nakaya
Y
Y
Kido
H
H
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001381:Azepines / Q000494:pharmacology; D053818:Chymases; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins / Q000494:pharmacology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D012697:Serine Endopeptidases / Q000378:metabolism*; D013552:Swine; D014132:Trachea / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D010880:Piperidines; D011498:Protein Precursors; D014662:Vasoconstrictor Agents; C083116:BQ 485; C086539:BQ 788; D012697:Serine Endopeptidases; D053818:Chymases