PMID- 17949903
OWN - NLM
STAT- MEDLINE
DCOM- 20080326
LR  - 20131121
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 428
IP  - 2-3
DP  - 2007 Nov 27
TI  - Acceleration of serotonin transporter transport-associated current by 
      3,4-methylenedioxymethamphetamine (MDMA) under acidic conditions.
PG  - 72-6
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) selectively releases serotonin (5-HT) 
      from neurons after uptake by the serotonin transporter (SERT) and causes 
      psychostimulant effects accompanied by hyperthermia. Since rapid increases in CNS 
      lactate levels are suggested in response to MDMA, we investigated the effects of 
      the physiologically-relevant increase in H(+) concentration on the two conducting 
      states of SERT expressed in Xenopus oocytes. Perfusion with SERT substrates at pH 
      7.4 dose-dependently evoked a transport-associated inward current response with 
      the following rank order of potency: 5-HT>MDMA>dopamine>>norepinephrine. In the 
      absence of transport substrates, a step hyperpolarization pulse activated a 
      transient Na(+) leak current, which was inhibited by SERT substrates with the 
      same rank, as well as by a SERT inhibitor, citalopram. At pH 6.4, the K(m) values 
      of 5-HT and dopamine for the transport-associated current were not altered, while 
      that of MDMA was three-fold lower. In contrast, the K(i) values of all these 
      substrates for transient leak current were unchanged at pH 6.4, suggesting that 
      the affinities to SERT binding sites are not influenced. These results suggest 
      that the effect of MDMA on SERT is enhanced by acidic conditions.
FAU - Yamauchi, Yosuke
AU  - Yamauchi Y
AD  - Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, 
      Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
FAU - Izumi, Takaya
AU  - Izumi T
FAU - Unemura, Kazuhiro
AU  - Unemura K
FAU - Uenishi, Yoshie
AU  - Uenishi Y
FAU - Nakagawa, Takayuki
AU  - Nakagawa T
FAU - Kaneko, Shuji
AU  - Kaneko S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070926
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Protons)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Sodium Channels)
RN  - 333DO1RDJY (Serotonin)
RN  - 33X04XA5AT (Lactic Acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Binding Sites/drug effects/physiology
MH  - Binding, Competitive/drug effects/physiology
MH  - Biological Transport, Active/drug effects/physiology
MH  - Brain/drug effects/metabolism/physiopathology
MH  - Dopamine/metabolism/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Hydrogen-Ion Concentration
MH  - Lactic Acid/metabolism
MH  - Membrane Potentials/drug effects/physiology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Neurons/drug effects/metabolism
MH  - Norepinephrine/metabolism/pharmacology
MH  - Oocytes
MH  - Protons
MH  - Rats
MH  - Serotonin/*metabolism/pharmacology
MH  - Serotonin Agents/*pharmacology
MH  - Serotonin Antagonists/pharmacology
MH  - Serotonin Plasma Membrane Transport Proteins/*drug effects/genetics/*metabolism
MH  - Sodium Channels/drug effects/metabolism
MH  - Xenopus laevis
EDAT- 2007/10/24 09:00
MHDA- 2008/03/28 09:00
CRDT- 2007/10/24 09:00
PHST- 2007/07/04 00:00 [received]
PHST- 2007/09/14 00:00 [revised]
PHST- 2007/09/19 00:00 [accepted]
PHST- 2007/10/24 09:00 [pubmed]
PHST- 2008/03/28 09:00 [medline]
PHST- 2007/10/24 09:00 [entrez]
AID - S0304-3940(07)01026-9 [pii]
AID - 10.1016/j.neulet.2007.09.037 [doi]
PST - ppublish
SO  - Neurosci Lett. 2007 Nov 27;428(2-3):72-6. doi: 10.1016/j.neulet.2007.09.037. Epub 
      2007 Sep 26.