Lack of Endothelin ETBReceptor Binding and Function in the Rat with a Mutant ETBReceptor Gene

Abstract Congenital aganglionosis rat is a mutant with an autosomal recessive gene ( sl ). Recent studies have revealed that the endothelin ET B receptor gene of sl / sl rat has a deletion of 301-bp region spanning exon 1 and intron 1 corresponding to the first and the second transmembrane domains of the receptor. In the present experiments, we examined the functions of ET B receptors in the sl / sl rats. In the membranes of cerebellum, heart, and lung of control (+/+ and sl /+) rats, ET-1 induced a monophasic, competitive displacement of [ 125 I]ET-1 binding, whereas ET-3, IRL 1620, and BQ-123 showed biphasic displacement. In the membranes of sl / sl rats, in contrast, ET-1, BQ-123, ET-3, and IRL 1620 showed only monophasic displacement. Scatchard analysis revealed a single [ 125 I]ET-3 binding site in the membrane of control heart but not in the sl / sl rat heart, and the specific binding sites for [ 125 I]ET-1 in both control and sl / sl rat hearts. In the control rat aorta but not in the sl / sl rat aorta, ET-3 induced endothelium-dependent relaxation. These results suggest that sl / sl rats do not have functional ET B receptors.