Plasticity in serotonin control mechanisms in the gut.
5-hydroxytryptamine (5-HT or serotonin) is a charged molecule and must be transported across biological membranes. Enzymes that catabolize 5-HT are all intracellular; therefore, 5-HT inactivation requires a high affinity transporter, known as serotonin transporter (SERT or 5-HTT). In the central and enteric nervous systems, SERT is located in serotonergic neurons; however, these neurons are not present in the gastrointestinal mucosa, where 5-HT initiates peristaltic and secretory reflexes. Instead, SERT is expressed by enterocytes. The severity of gastrointestinal effects caused by drugs that inhibit SERT, such as tricyclic antidepressants, selective serotonin reuptake inhibitors and cocaine, does not usually prevent their therapeutic or recreational use because backup transporters and alterations in receptor gene expression allow the gut to adapt, albeit imperfectly, to their toxicity.
Gershon
Michael D
MD
Department of Anatomy and Cell Biology, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA. mdg4@columbia.edu
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D017615:Enteric Nervous System / Q000502:physiology; D004759:Enterochromaffin Cells / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin