ABSENCE OF ETB-MEDIATED CONTRACTION IN PIEBALD-LETHAL MICE

Activation of the endothelin (ET) ET B receptor can mediate opposite effects, endothelium-dependent vasodilation but also direct vasoconstriction. So far one gene encoding an ET B receptor has been identified and associated with endothelium-dependent relaxation. It has been suspected that the presence of another ET B gene could explain ET B - 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 ET B receptor gene, whether ET B receptor-mediated constriction is lost. Piebald-lethal (s 1 ) mice, in contrast to control mice, completely lacked ET B specific ligand binding. The pressor effect of the ET B receptor selective agonist sarafotoxin S6c was completely absent. In vitro, contraction of stomach strips induced by sarafotoxin S6c was also abolished in Piebald-lethal (s 1 ) mice. These results demonstrate the responsibility of the known ET B receptor gene in ET B -mediated constriction.