Sandbox 77: Difference between revisions

<scene name='71/716548/5-ht3_receptor/1'>The 5-HT3 receptor</scene> is a pentameric cation-selective ion channel and plays a role in neuronal excitation to release neurotransmitters from the postsynaptic neuron. Opening of the cation channel causes an influx of sodium and calcium through the receptor pore leading to a membrane depolarization. Five receptor subunits, A to E, have been found in humans but only subunits A and B have been found in rodents. When experimentally expressed in a host, the 5-HT3 receptor is comprised of either A or AB subunits which can result in a homopentameric receptor or a heteropentameric receptor respectively. The A and B subunits are found throughout the brain in areas such as the hippocampus and amygdala. 5-HT3 is a transmembrane channel that is stimulated to open state by the interaction of the receptor with serotonin in the extracellular space.<ref>Hassaine G,Cedric D, Luigino G, Romain W, Menno BT, Ruud H, Alexandra G, Henning S, Takashi T, Aline D, Christophe M, Xiao-Dan L, Frederic P, Horst V, Hugues N. ''X-ray Structure of the Mouse Serotonin 5-HT3 Receptor. Nature 512.7514 (2014): 276-81.[http://www.nature.com/nature/journal/v512/n7514/full/nature13552.html DOI:10.1038/nature13552]</ref> The binding site is comprised of six loops from two adjacent subunits in the extracellular N-terminal domain. Loops A, B and C form the principal subunit and contain the <scene name='71/716548/5-ht3/1'>important side chains</scene> N128, W183 and Y234. Loops D, E and F form the complementary subunit of the binding site and contain the important side chains W90, Y143 and W195. The transmembrane region is comprised of multiple alpha helical structures and mediates ion flow and ion specificity.<ref name = two> Thompson AJ, Lummis SCR. 5-HT3 Receptors. Curr Pharm Des. 2006; 12(28): 3615–3630. PMID:2664614 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664614/]</ref>

Lysergic Acid Diethylamide, more commonly known as LSD, is a potent hallucinogen and is derived from ergotamine, an ergopeptine whose structural skeleton is contained in a diverse range of alkaloids. LSD acts as a non-selective 5-HT receptor agonist, meaning it can bind with equal affinity to two or more sub-types of 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. The docking is stabilized by all the same residues involved in normal binding in the orthosteric pocket. Hydrogen bonding between the amino group of the 5-membered ring of LSD and the T140 residue of the 5-HT2B receptor, as well as hydrogen bonding between D135 and the other ergoline amino group of LSD interacting in a similar fashion that 5-HT would bind to the receptor. <ref name = "one" />