akdov (Stranger) 09-22-03 11:09 No 460422				Tryptamine Recognition by Serotonin Transporters (Rated as: excellent)
						Found this completely randomly! Interactions of Tryptamine Derivatives with Serotonin Transporter Species Variants Implicate Transmembrane Domain I in Substrate Recognition Erika M. Adkins, Eric L. Barker, and Randy D. Blakely Mol Pharmacol 59(3), 514–523 (2001) (http://molpharm.aspetjournals.org/cgi/content/abstract/59/3/514) Medline (PMID=11179447) Abstract The serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT) is responsible for the inactivation of synaptic 5-HT and is also a target for multiple psychostimulants. Despite the critical role of SERT in 5-HT inactivation and psychostimulant response, many aspects of the transporter’s recognition of ligands are poorly defined. We took advantage of sequence divergence of SERT species variants to identify structural determinants of substrate recognition. Tryptamine derivatives with substitutions at the 4 and 7 positions on the phenyl ring, the indole nitrogen, and the b position show up to 40-fold potency differences for inhibiting [3H]5-HT transport in cells transfected with either human or Drosophila melanogaster SERT cDNAs. Species selectivities of these derivatives were largely recapitulated in antagonist binding. Human/D. melanogaster SERT chimera studies implicated the first two SERT transmembrane domains (TMDs) in the potency of the indole nitrogen-substituted compounds N-isopropyltryptamine (NIT), 5-methoxy-N-isopropyltryptamine (5-MNIT), and the 7-substituted compound 7-benzyloxytryptamine(7BT). Potency differences of analogs with substitutions at the 4 and b positions are influenced by sequences distal to this region. Within TMD I-II, species-scanning mutagenesis implicated a single residue (Y95 in human SERT, F90 in D. melanogaster SERT) in the recognition of NIT, 5-MNIT, and 7BT. Remarkably, this is the same site we established previously in species-specific recognition of the antagonists citalopram and mazindol. These findings support a critical role for TMD I residues in defining shared aspects of SERT substrate and antagonist recognition. Full article at http://chemakdov.tripod.com/Adkins.pdf brewed and canned in the UK
		Lilienthal (Moderator) 09-22-03 13:44 No 460443				Very interesting. It shows that DMT inhibits /
						Very interesting. It shows that DMT inhibits / releases serotonin at about the same concentrations as it activates the 5-HT2A receptor...
		Lego (Hive Bee) 09-22-03 16:10 No 460462				This article is great!
						Could you please post the complete reference the next time, so TFSE will find it more easily? Reference for Post 460422 (akdov: "Tryptamine Recognition by Serotonin Transporters", Tryptamine Chemistry): Mol. Pharmacol., 2001, 59(39), 514-523 Medline (PMID=11179447) This article is for free either as HTML or PDF at http://molpharm.aspetjournals.org/cgi/content/abstract/59/3/514 Edit: Thanks Lego, I have now edited the post at the top to include this. /Rhodium The candle that burns twice as bright burns half as long