Pseudo-Noncompetitive Antagonism by BQ123 of Intracellular Calcium Transients Mediated by Human ETA Endothelin Receptor

A. Sakamoto, Masashi Yanagisawa, G. Tsujimoto, K. Nakao, T. Toyooka, T. Masaki

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The family of endothelins, endothelin-1 (ET-1), ET-2 and ET-3, act on two subtypes of receptors called ETA and ETB receptors. BQ123 is an ETA-selective competitive antagonist. In this study, however, BQ123 inhibited ET-1-induced transients of cytosolic Ca2+ concentrations ([Ca2+]i) in an apparently noncompetitive manner in mouse L cell stably expressing cloned human ETA receptor. BQ123 (3 - 30 nM) did not change the EC50 of ET-1 (6.6 nM), but reduced the maximum responses down to 15.0 %. In an non-equilibrium binding assay which mimicks the conditions of [Ca2+]i transient assay (cells were incubated with [125I]ET-1 only for 30 s), BQ123 (30 nM) constantly decreased the specific [125I]ET-1 binding to (equivalent to)13% of that without the antagonist. Thus, the apparent noncompetitive antagonism by BQ123 of ETA receptor-mediated [Ca2+]i transient is due to the assay condition where the interactions of the agonist, antagonist and receptor remained non-equilibrium state.

Original languageEnglish (US)
Pages (from-to)679-686
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume200
Issue number2
DOIs
StatePublished - Jan 1 1994

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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