Binding of a new bioactive 31-amino-acid endothelin-1 to an endothelin ET(B) or ET(B)-like receptor in porcine lungs.
Endothelin-1-(1-31) is a new bioactive 31-amino-acid-length peptide generated from big endothelin-1 by chymase or other chymotrypsin-type proteases with various pathophysiologic functions. In this study, we have detected the specific and monophasic binding of [125I]endothelin-1-(1-31) in porcine lung membranes. Competition studies of [125I]endothelin-1-(1-31) binding by unlabeled endothelin-1-(1-31), endothelin-1, endothelin-3, and antagonists and agonists of endothelin ET(A) and ET(B) receptors suggest that the binding protein is an endothelin ET(B) or ET(B)-like receptor rather than an endothelin ET(A) receptor in porcine lungs. Kinetic studies showed that the affinity of endothelin-1-(1-31) to its receptor was approximately one order of magnitude lower than that of endothelin-1, and that the specific binding of endothelin-1-(1-31) was about 19% of endothelin-1 binding. The binding of [125I]endothelin-1-(1-31) was extremely slow, slower even than that of endothelin-1, and nearly irreversible. This unique quasi-irreversibility may explain the slow-onset and long-lasting biologic effects of this peptide in vivo.
Kitamura
Hiroko
H
Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Kuramoto-cho 3-18-15, Tokushima 770-8503, Japan.
Cui
Ping
P
Sharmin
Saimoon
S
Yano
Mihiro
M
Kido
Hiroshi
H
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D019334:Endothelin-3 / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D007457:Iodine Radioisotopes; D008168:Lung / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism*; D013552:Swine
D019332:Endothelin-1; D019334:Endothelin-3; D004791:Enzyme Inhibitors; D006020:Glycopeptides; D007457:Iodine Radioisotopes; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D010880:Piperidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C114932:endothelin-1 (1-31); C086539:BQ 788; D008666:Metalloendopeptidases; C072247:cyclo(Trp-Asp-Pro-Val-Leu); C008890:phosphoramidon