Dissociation Characteristics of Endothelin Receptor Agonists and Antagonists in Cloned Human Type-B Endothelin Receptor
| Autor: | Terry J. Opgenorth, Jinshyun R. Wu-Wong, W. J. Chiou, S. Sundy, S R Magnuson, Douglas B. Dixon |
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| Rok vydání: | 1997 |
| Předmět: |
Endothelin Receptor Antagonists
Endothelin receptor type A Physiology Recombinant Fusion Proteins CHO Cells Beta-1 adrenergic receptor Cricetinae Enzyme-linked receptor Animals Humans Receptor Glucagon-like peptide 1 receptor Protease-activated receptor 2 Sulfonamides Receptors Endothelin Chemistry Endothelins Cell Biology General Medicine Receptor Endothelin B Molecular biology Endothelin 1 Peptide Fragments Molecular Weight Kinetics Pyrimidines Endothelin receptor Oligopeptides Protein Binding |
| Zdroj: | Endothelium. 5:179-189 |
| ISSN: | 1029-2373 1062-3329 |
| DOI: | 10.3109/10623329709053397 |
| Popis: | The human type-B endothelin receptor (h-ETB) was cloned from human lung poly A+RNA and stably expressed in CHO cells. Endothelin (ET) receptor binding and stimulation of PI hydrolysis demonstrated that the cloned h-ETB receptor is functional and linked to intracellular signal transduction pathways in CHO cells. The molecular mass of the h-ETB receptor was determined to be 65 KDa, and Bmax and Kd were 0.36 pmol/mg and 80 pM, respectively. Competition studies employing receptor ligands revealed that the potencies of the test ligands (IRL1620, PD142893, and Ro46-2005) were dependent on the length of the incubation time, whereas the natural agonists (ET-1 and ET-3) were not. When competing with ET-1 in the h-ETB receptor binding, the IC50 increased from 1.2 nM to 8.2 nM for IRL1620, 0.068 microM to 1.9 microM for PD142893, and 0.76 microM to 12.7 microM for Ro46-2005, as the incubation time increased from 1 hr to 24 hr. These time-induced changes are likely due to differences in the dissociation characteristics between the artificial ligands and the natural ligands. |
| Databáze: | OpenAIRE |
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