Sandbox 77: Difference between revisions
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== Structural highlights/Specific Function of 5-HT2B== | == Structural highlights/Specific Function of 5-HT2B== | ||
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" /> | 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" /> | ||
== Structural highlights/Specific Function of 5-HT3== | == Structural highlights/Specific Function of 5-HT3== | ||
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Lysergic Acid Diethylamide, more commonly known as LSD, is a potent hallucinogen and non-selective 5-HT receptor agonist, meaning it can bind with equal affinity to two or more receptors. LSD actively binds in the orthosteric binding pocket to both the 5-HT1B and 5HT-2B receptors, suggesting a similar chemical structure and function between the two receptor families <ref name = "one" />. The docking is stabilized by hydrogen bonding between the amino group of the 5-membered ring of LSD and the threonine residue of the 5-HT1B receptor, in a similar fashion that 5-HT would bind to said receptor. | Lysergic Acid Diethylamide, more commonly known as LSD, is a potent hallucinogen and non-selective 5-HT receptor agonist, meaning it can bind with equal affinity to two or more receptors. LSD actively binds in the orthosteric binding pocket to both the 5-HT1B and 5HT-2B receptors, suggesting a similar chemical structure and function between the two receptor families <ref name = "one" />. The docking is stabilized by hydrogen bonding between the amino group of the 5-membered ring of LSD and the threonine residue of the 5-HT1B receptor, in a similar fashion that 5-HT would bind to said receptor. | ||
==5-HT3 receptor antagonist: 4i (N-(3-chloro-2-methylphenyl)quinoxalin-2-carboxamide)== | |||
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> | |||
==References== | ==References== | ||
