Hallucinogens induce a specific barcode of phosphorylation on the serotonin2A receptor that underlies a weaker receptor desensitization and internalization
Receptors & Clinical Investigation September 27, 2014 DOI: 10.14800/rci.230 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Keywords | Internalization Desensitization medicine Receptor Phosphorylation Cell biology |
| Citations | 1 |
| Key findings | Hallucinogenic agonists cause biased phosphorylation of the 5-HT2A receptor, resulting in weaker receptor desensitization and internalization than non-hallucinogenic agonists. |
Abstract
The serotonin (5-Hydroxytryptamine, 5-HT) 2A receptor represents one of the most striking examples where functional selectivity (or ligand-biased signaling) is transduced in distinct behaviours. This receptor is the primary target of psychedelic hallucinogens such as lysergic acid diethylamine, mescaline and psilocybin, which reproduce some of the core symptoms of schizophrenia and are often used to probe the disease. Why only some 5-HT 2A receptor agonists exhibit hallucinogenic activity, whereas structurally related agonists with comparable affinity and agonist activity (e.g. lisuride and ergotamine) lack such a psychoactive activity remains an incompletely resolved paradox. In a recent paper published in Molecular and Cellular Proteomics (doi: 10.1074/mcp.M113.036558) we demonstrated a biased phosphorylation of the 5-HT 2A receptor in response to hallucinogenic versus non-hallucinogenic agonists that leads to a weaker receptor desensitization and internalization by hallucinogens.