Transmembrane domains serotonin transporter

Adkins, E. M., Barker, E. L., and Blakely, R. D. (2001) Interactions of tryptamine derivatives with serotonin transporter species variants implicate transmembrane domain I in substrate recognition. Mol. Pharmacol. 59, 514-523. 

Chen, J. G., Sachpatzidis, A., and Rudnick, G. (1997) The third transmembrane domain of the serotonin transporter contains residues associated with substrate and cocaine binding. J. 

SNRIs bind both the serotonin and the norepinephrine transporters. The NET is structurally very similar to the 5-HT transporter. Like the serotonin transporter, it is a 12-transmembrane domain complex that allosterically binds norepinephrine. The NET also has a moderate affinity for dopamine. 

Just H, Sitte HH, Schmid JA, Freissmuth M, Kudlacek O (2004) Identification of an additional interaction domain in transmembrane domains 11 and 12 that supports oligomer formation in the human serotonin transporter. J Biol Chem 279 6650-6657 Keller NR, Diediich A, Appalsamy M, Miller LC, Caron MG, McDonald MP, Shelton RC, Blakely RD, Robertson D (2006) Norepinephrine transporter-deficient mice respond to anxiety producing and fearful environments with bradycardia and hypotension. Neuroscience 139 931-946... 

Henry LK, Adkins EM, Han Q, Blakely RD. Serotonin and cocaine-sensitive inactivation of human serotonin transporters by methanethiosulfonates targeted to transmembrane domain I. J. Biol. Chem. 2003 278 37052-37063. 

In addition to its receptors, serotonin has transporter molecules and there are alkaloids that interfere with the transport and uptake process. DNA s for serotonin transporters of rat leukemia cells have been cloned and sequenced. One of them has a 653 residue protein with 12-13 transmembrane domains. Interestingly they show considerable homology with transporters of some other transmitter substances and are sensitive to cocaine, reserpine and several other alkaloids [229,230,231,232]. Thus the inhibitory action of serotonin can be reduced not only by substances that act on its receptor but also by substances that hinder its access to the receptor [233]. 

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