PMID- 16185723
OWN - NLM
STAT- MEDLINE
DCOM- 20060310
LR  - 20221207
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 49
IP  - 6
DP  - 2005 Nov
TI  - Serotonin-transporter mediated efflux: a pharmacological analysis of amphetamines 
      and non-amphetamines.
PG  - 811-9
AB  - The physiological function of neurotransmitter transporter proteins like the 
      serotonin transporter (SERT) is reuptake of neurotransmitter that terminates 
      synaptic serotoninergic transmission. SERT can operate in reverse direction and 
      be induced by SERT substrates including 5-HT, tyramine and the positively charged 
      methyl-phenylpyridinium (MPP(+)), as well as the amphetamine derivatives 
      para-chloroamphetamine (pCA) and methylene-dioxy-methamphetamine (MDMA). These 
      substrates also induce inwardly directed sodium currents that are predominantly 
      carried by sodium ions. Efflux via SERT depends on this sodium flux that is 
      believed to be a prerequisite for outward transport. However, in recent studies, 
      it has been suggested that substrates may be distinct in their properties to 
      induce efflux. Therefore, the aim of the present study was a pharmacological 
      characterization of different SERT substrates in uptake experiments, their 
      abilities to induce transporter-mediated efflux and currents. In conclusion, the 
      rank order of affinities in uptake and electrophysiological experiments correlate 
      well, while the potencies of the amphetamine derivatives for the induction of 
      efflux are clearly higher than those of the other substrates. These discrepancies 
      can be only explained by mechanisms that can be induced by amphetamines. 
      Therefore, based on our pharmacological observations, we conclude that 
      amphetamines distinctly differ from non-amphetamine SERT substrates.
FAU - Hilber, Birgit
AU  - Hilber B
AD  - Institute of Pharmacology, Medical University Vienna, Waehringerstr. 13a, A-1090 
      Vienna, Austria.
FAU - Scholze, Petra
AU  - Scholze P
FAU - Dorostkar, Mario M
AU  - Dorostkar MM
FAU - Sandtner, Walter
AU  - Sandtner W
FAU - Holy, Marion
AU  - Holy M
FAU - Boehm, Stefan
AU  - Boehm S
FAU - Singer, Ernst A
AU  - Singer EA
FAU - Sitte, Harald H
AU  - Sitte HH
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050926
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 10028-17-8 (Tritium)
RN  - 333DO1RDJY (Serotonin)
RN  - CK833KGX7E (Amphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - X8ZC7V0OX3 (Tyramine)
SB  - IM
MH  - Amphetamine/*pharmacology
MH  - Biological Transport/drug effects
MH  - Cell Line
MH  - Dopamine Uptake Inhibitors/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Electric Stimulation/methods
MH  - Humans
MH  - Membrane Potentials/drug effects/physiology/radiation effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology
MH  - Patch-Clamp Techniques/methods
MH  - Serotonin/*metabolism
MH  - Serotonin Agents/pharmacology
MH  - Serotonin Plasma Membrane Transport Proteins/*physiology
MH  - Selective Serotonin Reuptake Inhibitors/pharmacokinetics/pharmacology
MH  - Time Factors
MH  - Transfection
MH  - Tritium/pharmacokinetics
MH  - Tyramine/pharmacokinetics
EDAT- 2005/09/28 09:00
MHDA- 2006/03/11 09:00
CRDT- 2005/09/28 09:00
PHST- 2005/05/18 00:00 [received]
PHST- 2005/08/10 00:00 [accepted]
PHST- 2005/09/28 09:00 [pubmed]
PHST- 2006/03/11 09:00 [medline]
PHST- 2005/09/28 09:00 [entrez]
AID - S0028-3908(05)00314-X [pii]
AID - 10.1016/j.neuropharm.2005.08.008 [doi]
PST - ppublish
SO  - Neuropharmacology. 2005 Nov;49(6):811-9. doi: 10.1016/j.neuropharm.2005.08.008. 
      Epub 2005 Sep 26.