Author Topic: Tryptamine Recognition by Serotonin Transporters  (Read 4902 times)

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akdov

  • Guest
Tryptamine Recognition by Serotonin Transporters
« on: September 22, 2003, 11:09:00 AM »
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




Lilienthal

  • Guest
Very interesting. It shows that DMT inhibits /
« Reply #1 on: September 22, 2003, 01:44:00 PM »
Very interesting. It shows that DMT inhibits / releases serotonin at about the same concentrations as it activates the 5-HT2A receptor...

Lego

  • Guest
This article is great!
« Reply #2 on: September 22, 2003, 04:10:00 PM »
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