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| Content Provider | PubMed Central |
|---|---|
| Author | Pheng, Leng Hong Dumont, Yvan Fournier, Alain Chabot, Jean-guy Beaudet, Alain Quirion, Rémi |
| Copyright Year | 2003 |
| Abstract | Neuropeptide Y Y1 receptors are known to internalize following the binding of agonists. In the present study, a pseudopeptide Y1 receptor antagonist, homodimeric Ile-Glu-Pro-Dpr-Tyr-Arg-Leu-Arg-Tyr-CONH2 (GR231118), also induced Y1 receptor internalization in human embryonic kidney (HEK293) cells. We demonstrated first that both specifically bound radiolabeled antagonist ([125I]GR231118) and agonist ([125I][Leu31, Pro34]PYY) underwent receptor-mediated sequestration/internalization in transfected HEK293 cells. Agonist-induced Y1 receptor internalization was dependent on clathrin-coated pits and was regulated in part by Gi/o-protein activation as revealed by pertussin toxin sensitivity. In contrast, antagonist-induced sequestration of Y1 receptors was partly dependent on clathrin-coated pits, but independent from Gi/o-protein activation. Exposure to high concentrations of agonist or antagonist caused a 50 and 75% loss of cell surface binding, respectively. The loss caused by the agonist rapidly recovered. This phenomenon was blocked by monensin, an inhibitor of endosome acidification, suggesting that cell surface receptor recovery is due to recycling. In contrast to the agonist, GR231118 induced a long-lasting sequestration of Y1 receptors in HEK293 cells. Immunofluorescence labeling indicated that following 40 min of incubation with either the agonist or the antagonist, Y1 receptors followed markedly different intercellular trafficking pathways. Taken together, these findings provided evidence that a pseudopeptide Y1 receptor antagonist can induce long-lasting disappearance of cell surface receptors through a pathway distinct from the classical endocytic/recycling pathway followed by stimulation with an agonist. |
| Related Links | http://dx.doi.org/10.1038/sj.bjp.0705306 |
| Starting Page | 695 |
| File Format | |
| ISSN | 00071188 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 139 |
| Language | English |
| Publisher Date | 2003-06-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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