Sandbox 77: Difference between revisions

5-HT, Serotonin, receptors are found on the membrane of neurons in the central nervous system and peripheral nervous system. These receptors allow for the body to respond to serotonin and regulate many biological pathways. Serotonin, also known as 5 hydroxytryptamine, is an endogenous neurotransmitter made from tryptophan and is largely found in the gastrointestinal tract. It is known to regulate mood, appetite, digestion, circadian rhythm, learning and internal temperature regulation. It is can be an inhibitory or excitatory neurotransmitter that is released into the synaptic space and can bind to receptors on the postsynaptic neuron or be taken back up into the presynaptic neuron via Serotonin reuptake transporters.<ref>Goodsell D. "Serotonin Receptor." RCSB PDB-101 (2013) [http://www.rcsb.org/pdb/101/motm.do?momID=164 DOI: 10.2210/rcsb_pdb/mom_2013_8]</ref> 5-HT receptors are classified into 7 different subfamilies (5-HT1, 5-HT2, 5-HT3, etc.) by signaling mechanisms and homology of structure. All 5-HT receptors are known to have G-protein linked pathways except for the 5-HT3 receptor which acts as an ion channel. <ref name ="one">Wang C, Jiang Y, Ma J, Wu H, Wacker D, Katritch V, Han GW, Liu W, Huang XP, Vardy E, McCorvy JD, Gao X, Zhou EZ, Melcher K, Zhang C, Bai F, Yang H, Yang L, Jiang H, Roth BL, Cherezov V, Stevens RC, Xu HE. Structural Basis for Molecular Recognition at Serotonin Receptors. Science. 2013 May 3; 340(6132): 610–614. PMID:3644373 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644373/]</ref>

The <scene name='71/716548/5-ht2b_receptor/1'>5-HT2B receptor</scene> is important in utilizing serotonin signals to encourage proper development and continuing function of the cardiovascular system. Overexpression of 5-HT2B has been linked to congestive heart failure.<ref>Wiebke J, Schymura Y, Novoyatleva T, Kojonazarov B, Boehm M, Wietelmann A, Luitel H, Murmann K, Krompiec DR, Tretyn A, Pullamsetti SS, Weissmann N, Seeger W, Ghofrani HA, Schermuly RT. 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure. Biomed Res Int. 2015; 2015: 438403. PMID:4312574 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312574]</ref> 5-HT2B utilizes the alpha Gq protein pathway which triggers intracellular cGMP production through activation of nictric-oxidase synthase (NOS).<ref>Nebigil, Etienne, Schaerlinger, Hickel, Launay, Maroteaux "Developmentally Regulated Serotonin 5-HT2B Receptors.” [http://www.sciencedirect.com/science/article/pii/S0736574801000223 DOI: 10.1016/S0736-5748(01)00022-3]</ref> This receptor is also known for being the target of the drug LSD, which has similar structure to serotonin. <ref>Berumen LC, Rodriguez A, Miledi R, Gracia-Alcocer G. Serotonin Receptors in Hippocampus. ScientificWorldJournal. 2012;2012:823493. Epub 2012 May 2. PMID:3353568 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353568/]</ref> The structure of this receptor is much like that of 5-HT1B, however significant differences are seen in their binding pockets. The pocket of 5-HT1B is much broader than that of 5-HT2B, due to a 3 Å shift of the top of helix V. Perhaps this difference highlights a variation in serotonin affinity between the two families. It has the characteristic 7 alpha helices and the N-terminus sticks out into extracellular space. <ref name="one" />

A 5HT3 antagonist shown to act as an antidepressant in diabetes-induced depression in mice; it resulted in a significant decrease in 5HT in the midbrain after administration. <ref>Gupta D, Devadoss T, Mahesh R. "A novel 5HT 3 antagonist 4i (N-(3-chloro-2-methylphenyl) quinoxalin-2-carboxamide) prevents diabetes-induced depressive phenotypes in mice: Modulation of serotonergic system." Behavioural brain research 297 (2016): 41-50. [http://www.sciencedirect.com/science/article/pii/S0166432815302217 DOI:10.1016/j.bbr.2015.10.007]</ref>