ABSENCE OF ETB-MEDIATED CONTRACTION IN PIEBALD-LETHAL MICE

Activation of the endothelin (ET) ETB receptor can mediate opposite ef fects, endothelium-dependent vasodilation but also direct vasoconstric tion. So far one gene encoding an ETB receptor has been identified and associated with endothelium-dependent relaxation. It has been suspect ed that the presence of another ETB gene could explain ETB - mediated contraction. The goal of the present study was to evaluate in Piebald- lethal (s(1)) mice, a naturally occurring mutant with deletion of the known ETB receptor gene, whether ETB receptor-mediated constriction is lost. Piebald-lethal (s(1)) mice, in contrast to control mice, comple tely lacked ETB specific ligand binding. The presser effect of the ETB receptor selective agonist sarafotoxin S6c was completely absent. In vitro, contraction of stomach strips induced by sarafotoxin S6c was al so abolished in Piebald-lethal (s(1)) mice. These results demonstrate the responsibility of the known ETB receptor gene in ETB-mediated cons triction.