Functional analysis of five endothelin-B receptor mutations found in human hirschsprung disease patients

Yoichiro Abe, Takeshi Sakurai, Takahisa Yamada, Toshiaki Nakamura, Masashi Yanagisawa, Katsutoshi Goto

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Several missense mutations of the endothelin-B receptor (EDNRB) associated with Hirschsprung disease have recently been identified. Five mutated EDNRB (A183G, W276C, R319W, M374I and P383L) cDNAs were transiently expressed in several cell lines to examine the effects of these mutations. Ligand-receptor binding experiments demonstrated that all mutants examined here accept endothelins with a high affinity. Especially, the affinity of endothelins to P383L was increased. However, the number of binding sites of A183G, W276C and P383L was markedly decreased. The subcellular localization of these mutant receptors was the same as that of wild-type EDNRB, whereas the amount of protein of each mutant receptor was decreased. All mutant receptors were impaired in intracellular Ca2+ mobilization. These findings indicate that these missense mutations result in loss of function of EDNRB, and may provide the molecular pathological basis of Hirschsprung disease in some individuals. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)524-531
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Aug 28 2000


  • Endothelin
  • Endothelin-B receptor
  • Hirschsprung disease
  • Intracellular Ca mobilization
  • Missense mutations

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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