PMID- 15115888
OWN - NLM
STAT- MEDLINE
DCOM- 20050105
LR  - 20141120
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 80
IP  - 2
DP  - 2004 Aug
TI  - PCB-induced inhibition of the vesicular monoamine transporter predicts reductions 
      in synaptosomal dopamine content.
PG  - 288-95
AB  - Both Aroclor mixtures and individual non-coplanar polychlorinated biphenyl (PCB) 
      congeners reduce dopamine (DA) concentrations in cells in culture and in the 
      brains of developing and adult laboratory animals. These reductions may involve 
      inhibition of the dopamine transporter (DAT) and the vesicular monoamine 
      transporter (VMAT) responsible, respectively, for the uptake of extracellular DA 
      and the packaging of nerve terminal cytosolic DA into synaptic vesicles. However, 
      the relative contribution of each monoamine transporter to the PCB-induced 
      reductions in tissue DA has not been determined. Accordingly, we exposed striatal 
      synaptosomes from adult rats to individual PCB congeners, a commercial mixture of 
      PCBs or known monoamine transporter inhibitors; measured synaptosomal DA; and 
      related these changes to media DA and concentrations of 3,4-dihydroxyphenylacetic 
      (DOPAC). PCB-induced elevations in media DA concentrations are not sufficient to 
      explain the reductions in tissue DA because known DAT inhibitors elevate media DA 
      to a much greater extent than PCBs and yet induce similar decreases in tissue DA 
      concentrations. On the other hand, PCB-induced elevations in DOPAC, reflective of 
      increases in nerve terminal cytosolic DA, are sufficient to explain the 
      reductions in tissue DA, because a known VMAT inhibitor elevates DOPAC and 
      reduces tissue DA to an extent similar to that seen with PCBs. Taken together, 
      these results suggest that elevations in DOPAC, reflective of increases in nerve 
      terminal cytosolic DA due to VMAT inhibition, rather than elevations in media DA 
      due to DAT inhibition, are largely responsible for the observed decreases in 
      tissue DA content.
FAU - Bemis, Jeffrey C
AU  - Bemis JC
AD  - New York State Department of Health, Wadsworth Center, and School of Public 
      Health, University at Albany, Box 509, Albany, New York 12201-0509, USA.
FAU - Seegal, Richard F
AU  - Seegal RF
LA  - eng
GR  - 829390/PHS HHS/United States
GR  - ES11263/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040428
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Environmental Pollutants)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Modulators)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Solutions)
RN  - 0 (Vesicular Biogenic Amine Transport Proteins)
RN  - 0 (Vesicular Monoamine Transport Proteins)
RN  - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 3,4-Dihydroxyphenylacetic Acid/metabolism
MH  - Animals
MH  - Chromatography, High Pressure Liquid
MH  - Dopamine/*metabolism
MH  - Environmental Pollutants/*pharmacology
MH  - In Vitro Techniques
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Male
MH  - Membrane Glycoproteins/*antagonists & inhibitors
MH  - *Membrane Transport Modulators
MH  - Membrane Transport Proteins/*antagonists & inhibitors
MH  - Polychlorinated Biphenyls/*pharmacology
MH  - Rats
MH  - Rats, Long-Evans
MH  - Solutions
MH  - Synaptosomes/drug effects/*metabolism
MH  - Vesicular Biogenic Amine Transport Proteins
MH  - Vesicular Monoamine Transport Proteins
EDAT- 2004/04/30 05:00
MHDA- 2005/01/06 09:00
CRDT- 2004/04/30 05:00
PHST- 2004/04/30 05:00 [pubmed]
PHST- 2005/01/06 09:00 [medline]
PHST- 2004/04/30 05:00 [entrez]
AID - kfh153 [pii]
AID - 10.1093/toxsci/kfh153 [doi]
PST - ppublish
SO  - Toxicol Sci. 2004 Aug;80(2):288-95. doi: 10.1093/toxsci/kfh153. Epub 2004 Apr 28.