Lack of endothelin ETB receptor binding and function in the rat with a mutant ETB receptor gene

Biochem Biophys Res Commun. 1996 May 6;222(1):139-43. doi: 10.1006/bbrc.1996.0711.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine Vasopressin / pharmacology
  • Binding, Competitive
  • Cerebellum / metabolism
  • Disease Models, Animal
  • Endothelins / metabolism*
  • Lung / metabolism
  • Megacolon / genetics
  • Myocardium / metabolism
  • Rats
  • Rats, Mutant Strains
  • Receptor, Endothelin B
  • Receptors, Endothelin / genetics*
  • Receptors, Endothelin / physiology
  • Vasoconstriction / drug effects


  • Endothelins
  • Receptor, Endothelin B
  • Receptors, Endothelin
  • Arginine Vasopressin