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The Role of Membrane and Vesicular Monoamine Transporters in the Neurotoxic and Hypothermic Effects of 1-Methyl-4-
 

Summary: The Role of Membrane and Vesicular Monoamine Transporters
in the Neurotoxic and Hypothermic Effects of 1-Methyl-4-
(2 -aminophenyl)-1,2,3,6-tetrahydropyridine (2 -NH2-MPTP)
Adam L. Numis, Erica L. Unger, Douglas L. Sheridan, Angela C. Chisnell, and
Anne M. Andrews
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania
Received January 22, 2004; accepted June 11, 2004 This article is available online at http://molpharm.aspetjournals.org
ABSTRACT
The neurotoxin 1-methyl-4-(2 -aminophenyl)-1,2,3,6-tetrahydro-
pyridine (2 -NH2-MPTP) damages forebrain serotonin (5-HT) and
norepinephrine (NE) nerve terminals while sparing striatal dopa-
minergic innervation. Previous studies suggest that 2 -NH2-
MPTP acts by a mechanism that involves uptake by the plasma
membrane 5-HT and NE transporters. The present investigation
further explores the molecular mechanism of 2 -NH2-MPTP with
regard to cellular transport and effects on body temperature.
Mice with genetically controlled decreases in serotonin trans-
porter (SERT) expression were studied to corroborate pharma-
cologic evidence implicating SERT in 2 -NH2-MPTP-induced
serotonin neurotoxicity. To investigate whether sequestration by

  

Source: Andrews, Anne M. - Huck Institutes of the Life Sciences, Pennsylvania State University

 

Collections: Biology and Medicine