Lack of endothelin ETB receptor binding and function in the rat with a mutant ETB receptor gene.
Congenital aganglionosis rat is a mutant with an autosomal recessive gene (sl). Recent studies have revealed that the endothelin ETB 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 ETB 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 [125I]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 [125I]ET-3 binding site in the membrane of control heart but not in the sl/sl rat heart, and the specific binding sites for [125I]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 ETB receptors.
Karaki
H
H
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Japan. ahkrki@hongo.ecc.u-tokyo.ac.jp
Mitsui-Saito
M
M
Takimoto
M
M
Oda
K
K
Okada
T
T
Ozaki
T
T
Kunieda
T
T
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001667:Binding, Competitive; D002531:Cerebellum / Q000378:metabolism; D004195:Disease Models, Animal; D016232:Endothelins / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008531:Megacolon / Q000235:genetics; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D001127:Arginine Vasopressin