PMID- 17614110
OWN - NLM
STAT- MEDLINE
DCOM- 20071018
LR  - 20131121
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 223
IP  - 3
DP  - 2007 Sep 15
TI  - Methamphetamine and 3,4-methylenedioxymethamphetamine interact with central 
      nicotinic receptors and induce their up-regulation.
PG  - 195-205
AB  - Previous work from our group indicated that alpha7 nicotinic acetylcholine 
      receptors (alpha7 nAChR) potentially play a role in methamphetamine (METH) and 
      3,4-methylenedioxymethamphetamine (MDMA) neurotoxicity. The aims of the present 
      study were two-fold: (1) to demonstrate the interaction of METH and MDMA with 
      homomeric alpha7 nAChR ([(3)H]methyllycaconitine binding) and other heteromeric 
      subtypes ([(3)H]epibatidine binding); and (2) to show the effects of amphetamine 
      derivative pretreatment on the density of binding sites. METH and MDMA displaced 
      [(3)H]methyllycaconitine and [(3)H]epibatidine binding in membranes from 
      NGF-differentiated PC 12 cells and mouse brain, with K(i) values in the 
      micromolar range, MDMA revealing a greater affinity than METH. In addition, METH 
      and MDMA induced a time- and concentration-dependent increase in 
      [(3)H]methyllycaconitine and [(3)H]epibatidine binding; which had already been 
      apparent after 6 h of pretreatment, and which peaked in differentiated PC 12 
      cells after 48 h. The highest increases were found in [(3)H]epibatidine binding, 
      with MDMA inducing higher increases than METH. Treatment with METH and MDMA 
      increased B(max) of high-affinity sites for both radioligands without affecting 
      K(d). The heightened binding was inhibited by pretreatment with cycloheximide, 
      suggesting the participation of newly synthesised proteins while inhibition of 
      protein trafficking to plasma membrane did not block up-regulation. The effects 
      of protein kinase and cyclophilin inhibitors on such up-regulation were explored, 
      revealing a rapid, differential and complex regulation, similar to that described 
      for nicotinic ligands. All of these results demonstrate that METH and MDMA have 
      affinity for, and can interact with, nAChR, inducing their up-regulation, 
      specially when higher doses are used. Such effects may have a role in METH- and 
      MDMA-induced neurotoxicity, cholinergic neurotransmission, and in processes 
      related to addiction and dependence.
FAU - Garcia-Rates, Sara
AU  - Garcia-Rates S
AD  - Unitat de Farmacologia i Farmacognosia, Facultat de Farmacia, Nucli Universitari 
      de Pedralbes, Universitat de Barcelona, 08028 Barcelona, Spain.
FAU - Camarasa, Jordi
AU  - Camarasa J
FAU - Escubedo, Elena
AU  - Escubedo E
FAU - Pubill, David
AU  - Pubill D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070526
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Chrna7 protein, mouse)
RN  - 0 (Chrna7 protein, rat)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
RN  - 44RAL3456C (Methamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Binding, Competitive
MH  - *Brain/cytology/drug effects/metabolism
MH  - Cell Membrane/*drug effects/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Male
MH  - Methamphetamine/*pharmacology
MH  - Mice
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - PC12 Cells
MH  - Radioligand Assay
MH  - Rats
MH  - Receptors, Nicotinic/*biosynthesis
MH  - Time Factors
MH  - Up-Regulation
MH  - alpha7 Nicotinic Acetylcholine Receptor
EDAT- 2007/07/07 09:00
MHDA- 2007/10/19 09:00
CRDT- 2007/07/07 09:00
PHST- 2007/02/17 00:00 [received]
PHST- 2007/05/16 00:00 [revised]
PHST- 2007/05/19 00:00 [accepted]
PHST- 2007/07/07 09:00 [pubmed]
PHST- 2007/10/19 09:00 [medline]
PHST- 2007/07/07 09:00 [entrez]
AID - S0041-008X(07)00245-1 [pii]
AID - 10.1016/j.taap.2007.05.015 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2007 Sep 15;223(3):195-205. doi: 
      10.1016/j.taap.2007.05.015. Epub 2007 May 26.