Serotonin receptors and systems: endless diversity?

Abstract

Serotonin is probably unique among the monoamines in that its effects are subserved by as many as 13 distinct heptahelical, G protein-coupled receptors (GPCRs) and a ligand-gated ion channel family (5-HT3). These receptors are divided into seven distinct classes (5-HT, t o 5-HT,) largely on the basis of their structural, transductional and operational characteristics. While this degree of physical diversity clearly underscores the physiological importance of serotonin, evidence for an even greater degree of operational diversity continues to emerge. Here, we will review this diversity and its physiological and possibly pathophysiological consequences. Indeed, 5-HT research which is about 50 years old, has resulted in numerous therapeutic agents, some of which have a major impact on disease management. Thus, selective 5-HT reuptake inhibitors (SSRIs) are among the most widely used drugs in depression and other disorders such as anxiety, social phobia, panic disorders, or obsessive compulsive disorders (OCDs) to name a few. The discovery of 5-HT18/1D receptor agonists (the triptans) for treating migraine, 5-HT3 receptor antagonists for chemotherapy and radiation-induced emesis, and finally the emergence of 5-HT3/5-HT4 ligands to treat irritable bowel syndrome (IBS), all represent major advances in the field. Finally, the role of 5-HT in the mechanism of action of antipsychotic agents still is a topic of intense research, which promises better treatments for schizophrenia.