Binding of a new bioactive 31-amino-acid endothelin-1 to an endothelin ET B or ET B-like receptor in porcine lungs

Abstract

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.