A novel bioactive 31-amino acid endothelin-1 is a potent chemotactic peptide for human neutrophils and monocytes.
Endothelin (ET)-1(1-31) is a novel 31-amino acid-length peptide derived from big ET-1 by chymase or other chymotrypsin-type proteases and is a major ET derivative in human neutrophils. In this study, we revealed that ET-1(1-31), but not big ET, exhibited chemotactic activities toward human neutrophils and monocytes as an inflammatory mediator, although the effects were less potent than those of formyl-methionyl-leucyl-phenylalanine or interleukin-8. However, the chemotactic effects of ET-1(1-31) were much greater than those of the 21-amino acid ET-1, ET-1(1-21). Checkerboard analyses revealed that the effects are chemotactic rather than chemokinetic. The effects of ET-1(1-31) are not mediated by interleukin-8 or monocyte chemoattractant protein-1. The chemotactic effects and an increase in intracellular-free Ca(2)(+) caused by ET-1(1-31) were significantly inhibited by BQ123, an ET(A) receptor antagonist, but not by BQ788, an ET(B) receptor antagonist, suggesting that ET-1(1-31) mediates chemotaxis through an ET(A) or ET(A)-like receptor.
Cui
P
P
Division of Enzyme Chemistry, Institute for Enzyme Research, Third Department of Internal Medicine, and. Department of Pharmacology, School of Medicine, The University of Tokushima, Tokushima, Japan.
Tani
K
K
Kitamura
H
H
Okumura
Y
Y
Yano
M
M
Inui
D
D
Tamaki
T
T
Sone
S
S
Kido
H
H
D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000031:analogs & derivatives; D016232:Endothelins / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology / Q000502:physiology; D016209:Interleukin-8 / Q000494:pharmacology; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology
D018932:Chemokine CCL2; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D018836:Inflammation Mediators; D016209:Interleukin-8; D010446:Peptide Fragments; C419584:endothelin-1 (1-21); C114932:endothelin-1 (1-31); D002118:Calcium