PMID- 17936243
OWN - NLM
STAT- MEDLINE
DCOM- 20080320
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1778
IP  - 1
DP  - 2008 Jan
TI  - Uptake of 3,4-methylenedioxymethamphetamine and its related compounds by a 
      proton-coupled transport system in Caco-2 cells.
PG  - 42-50
AB  - 3,4-methylenedioxymethamphetamine (MDMA) is an illegal amphetamine-type stimulant 
      (ATS) that is abused orally in the form of tablets for recreational purposes. The 
      aim of this work is to investigate the absorption mechanism of MDMA and other 
      related compounds that often occur together in ATS tablets, and to determine 
      whether such tablet components interact with each other in intestinal absorption. 
      The characteristics of MDMA uptake by the human intestinal epithelial Caco-2 cell 
      line were investigated. The Michaelis constant and the maximal uptake velocity at 
      pH 6.0 were 1.11 mM and 13.79 nmol/min/mg protein, respectively, and the 
      transport was electroneutral. The initial uptake rate was regulated by both 
      intra- and extracellular pH. MDMA permeation from the apical to the basolateral 
      side was inferior to that in the reverse direction, and a decrease in apical pH 
      enhanced MDMA permeation from the basolateral to the apical side. These facts 
      indicate that this transport system may be an antiporter of H+. However, under 
      physiological conditions, the proton gradient cannot drive the MDMA uptake 
      because it is inwardly directed. Large concentration differences of MDMA itself 
      drive this antiporter. Various compounds with similar amine moieties inhibited 
      the uptake, but substrates of organic cation transporters (OCT1-3) and an 
      H+-coupled efflux antiporter, MATE, were not recognized.
FAU - Kuwayama, Kenji
AU  - Kuwayama K
AD  - National Research Institute of Police Science, 6-3-1, Kashiwanoha, Kashiwa, Chiba 
      277-0882, Japan. kuwayama@nrips.go.jp
FAU - Inoue, Hiroyuki
AU  - Inoue H
FAU - Kanamori, Tatsuyuki
AU  - Kanamori T
FAU - Tsujikawa, Kenji
AU  - Tsujikawa K
FAU - Miyaguchi, Hajime
AU  - Miyaguchi H
FAU - Iwata, Yuko
AU  - Iwata Y
FAU - Miyauchi, Seiji
AU  - Miyauchi S
FAU - Kamo, Naoki
AU  - Kamo N
FAU - Kishi, Tohru
AU  - Kishi T
LA  - eng
PT  - Journal Article
DEP - 20070908
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Protons)
RN  - 01Q9PC255D (Ammonium Chloride)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Ammonium Chloride/pharmacology
MH  - Caco-2 Cells
MH  - Humans
MH  - Hydrogen-Ion Concentration/drug effects
MH  - *Ion Transport/drug effects
MH  - Models, Biological
MH  - N-Methyl-3,4-methylenedioxyamphetamine/chemistry/*metabolism
MH  - Permeability/drug effects
MH  - *Protons
MH  - Regression Analysis
MH  - Time Factors
EDAT- 2007/10/16 09:00
MHDA- 2008/03/21 09:00
CRDT- 2007/10/16 09:00
PHST- 2007/04/15 00:00 [received]
PHST- 2007/08/24 00:00 [revised]
PHST- 2007/08/27 00:00 [accepted]
PHST- 2007/10/16 09:00 [pubmed]
PHST- 2008/03/21 09:00 [medline]
PHST- 2007/10/16 09:00 [entrez]
AID - S0005-2736(07)00333-1 [pii]
AID - 10.1016/j.bbamem.2007.08.023 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2008 Jan;1778(1):42-50. doi: 10.1016/j.bbamem.2007.08.023. 
      Epub 2007 Sep 8.