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ET A and ET B Specific Ligands Synergistically Antagonize Endothelin‐1 Binding to an Atypical Endothelin Receptor in Primary Rat Astrocytes
Author(s) -
Jensen Niels,
Hasselblatt Martin,
Sirén AnnaLeena,
Schilling Lothar,
Schmidt Martin,
Ehrenreich Hannelore
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70020473.x
Subject(s) - receptor , radioligand , ligand (biochemistry) , endothelin 1 , microbiology and biotechnology , binding site , endothelin receptor , endothelins , stereochemistry , agonist , chemistry , astrocyte , biology , biochemistry , endocrinology , central nervous system
Using a whole‐cell binding procedure with long incubations at low temperature and subsequent acid stripping, we have characterized an atypical endothelin (ET) receptor in primary rat cortical astrocyte cultures. We found the following: (a) no competition for 125 I‐ET‐1 binding by the ET A antagonists BQ‐123 and LU 135252 or the ET B agonist IRL 1620; (b) weak competition by the ET B antagonist BQ‐788 and by the predominant ET B ligand ET‐3; (c) potent synergistic competition of ET A and ET B ligands in combination for 125 I‐ET‐1 binding; (d) potent competition of ET‐1 with any of the radioligands used, 125 I‐ET‐1, 125 I‐IRL 1620, and [ 3 H]BQ‐123; (e) lack of competition of IRL 1620 and BQ‐123 with the respective other radioligand; (f) shifting of the amount of acid‐strippable 125 I‐ET‐1 binding from 20 to 80% by ET B ligands and to 4% by ET A ligands; and (g) as a control, typical ET A and ET B binding characteristics of the RAT‐1 fibroblast and the U373MG astrocytoma cell line, respectively, under our assay conditions. The unusual binding properties of astrocytic ET receptors described in this study appear to be the result of several binding sites in the receptor for different ET ligands or ligand epitopes.