ETA and ETB Specific Ligands Synergistically Antagonize Endothelin-1 Binding to an Atypical Endothelin Receptor in Primary Rat Astrocytes |
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Authors: | Niels Jensen,Martin Hasselblatt,Anna-Leena Siré n,Lothar Schilling,&dagger Martin Schmidt, Hannelore Ehrenreich |
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Affiliation: | Departments of Neurology and Psychiatry, Georg-August-University, and Max-Planck-Institute for Experimental Medicine, Göttingen;; Department of Neurosurgery, University Hospital, Mannheim;and; Main Laboratory, BASF Aktiengesellschaft, Ludwigshafen, Germany |
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Abstract: | Abstract: 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 125I-ET-1 binding by the ETA antagonists BQ-123 and LU 135252 or the ETB agonist IRL 1620; (b) weak competition by the ETB antagonist BQ-788 and by the predominant ETB ligand ET-3; (c) potent synergistic competition of ETA and ETB ligands in combination for 125I-ET-1 binding; (d) potent competition of ET-1 with any of the radioligands used, 125I-ET-1, 125I-IRL 1620, and [3H]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 125I-ET-1 binding from 20 to 80% by ETB ligands and to 4% by ETA ligands; and (g) as a control, typical ETA and ETB 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. |
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Keywords: | Primary astrocytes Rat Endothelin receptor ETA ETB Antagonists Binding sites |
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