Desensitization and internalization mechanisms of the 5‐HT4 receptors

The serotonin 5‐HT4 receptor is a member of the superfamily of G‐protein‐coupled receptors (GPCRs) that mediates many physiological effects in the central nervous system and its periphery. Recently, a 5‐HT4 receptor agonist was shown to produce faster antidepressant‐like response in animal models in comparison to conventional antidepressants, and this effect persists for at least 2 weeks of treatment without generating tolerance. Importantly, long‐term administration of various classes of antidepressants has been reported to induce desensitization and/or downregulation of 5‐HT4 receptors in brain areas implicated in the physiopathology of depression. These observations point to the importance of studying the mechanisms of desensitization and regulation of the 5‐HT4 receptors since they seem distinctively implicated in therapeutic response to the classical selective serotonin reuptake inhibitors (SSRIs) and novel faster acting antidepressants. Hence, desensitization and internalization mechanisms of the 5‐HT4 receptors have been characterized with special emphasis on the 5‐HT4a and 5‐HT4b isoforms. WIREs Membr Transp Signal 2012, 1:779–788. doi: 10.1002/wmts.52 For further resources related to this article, please visit the WIREs website .