Morphine-like activity of natural human IgG autoantibodies is because of binding to the first and third extracellular loops of the mu-opioid receptor
| Autor: | Gilles Dietrich, Gaëtane Macé, Catherine Blanpied, Laurent J. Emorine, P. Druet |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Agonist
medicine.drug_class Molecular Sequence Data Receptors Opioid mu Peptide Enzyme-Linked Immunosorbent Assay CHO Cells Biology Biochemistry Opioid receptor Cricetinae medicine Extracellular Enzyme-linked receptor Animals Humans Amino Acid Sequence Receptor Molecular Biology Autoantibodies chemistry.chemical_classification Binding Sites Morphine Cell Biology Molecular biology Transmembrane domain chemistry Immunoglobulin G Cyclase activity |
| Zdroj: | The Journal of biological chemistry. 274(29) |
| ISSN: | 0021-9258 |
| Popis: | We have previously demonstrated that randomly selected healthy individuals express anti-human μ-opioid receptor antibodies which behave as agonist in vitro. In this study, we show that the activity of these antibodies was not affected by the deletion of the amino-terminal region of the receptor. Using agarose-bound peptide columns, we affinity-purified IgG specifically directed toward each extracellular loop. Whatever its specificity, each anti-human μ-opioid receptor (hMOR) extracellular loop peptide IgG preparation was unable, when examined individually, to reduce adenylate cyclase activity. Activation of the hMOR was, however, achieved by the simultaneous binding of IgG to the first and third extracellular loops of the receptor. Our results suggest that the simultaneous binding of IgG antibodies to these two loops mimics morphine-induced receptor activation by triggering a coordinated shift of the third and sixth transmembrane helices. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|