Abstract
Congenital aganglionosis rat is a mutant with an autosomal recessive gene (sl). Recent studies have revealed that the endothelin ETBreceptor gene ofsl/slrat 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 ETBreceptors in thesl/slrats. In the membranes of cerebellum, heart, and lung of control (+/+ andsl/+) rats, ET-1 induced a monophasic, competitive displacement of [125I]ET-1 binding, whereas ET-3, IRL 1620, and BQ-123 showed biphasic displacement. In the membranes ofsl/slrats, in contrast, ET-1, BQ-123, ET-3, and IRL 1620 showed only monophasic displacement. Scatchard analysis revealed a single [125I]ET-3 binding site in the membrane of control heart but not in thesl/slrat heart, and the specific binding sites for [125I]ET-1 in both control andsl/slrat hearts. In the control rat aorta but not in thesl/slrat aorta, ET-3 induced endothelium-dependent relaxation. These results suggest thatsl/slrats do not have functional ETBreceptors.
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