Acrylamide inhibits dopamine uptake in rat striatal synaptic vesicles

Richard M. LoPachin, David S. Barber, Deke He, Soma Das

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Evidence suggests that acrylamide (ACR) neurotoxicity is mediated by decreased presynaptic neurotransmitter release. Defective release might involve disruption of neurotransmitter storage, and therefore, we determined the effects of in vivo and in vitro ACR exposure on 3H-dopamine (DA) transport into rat striatal synaptic vesicles. Results showed that vesicular DA uptake was decreased significantly in rats intoxicated at either 50 mg/kg/day × 5 days or 21 mg/kg/day × 21 days. ACR intoxication also was accompanied by a reduction in KCl-evoked synaptosomal DA release, although consistent changes in presynaptic membrane transport were not observed. Silver stain and immunoblot analyses suggested that reduced vesicular uptake was not due to active nerve terminal degeneration or to a reduction in the synaptic vesicle content of isolated striatal synaptosomes. Nor did the in vivo presynaptic effects of ACR involve changes in synaptosomal glutathione concentrations. In vitro exposure of striatal vesicles showed that both ACR and two sulfhydryl reagents, N-ethylmaleimide (NEM) and iodoacetic acid (IAA), produced concentration-dependent decreases in 3H-DA uptake. Although ACR was significantly less potent than either NEM or IAA, all three chemicals caused comparable maximal inhibitions of vesicular uptake. Kinetic analysis of DA uptake showed that in vitro exposure to either ACR or NEM decreased Vmax and increased Km. Determination of radiolabel efflux from 3H-DA-loaded vesicles indicated that in vitro ACR did not affect neurotransmitter retention. These data suggest that ACR impaired neurotransmitter uptake into striatal synaptic vesicles, possibly by interacting with sulfhydryl groups on functionally relevant proteins. The resulting disruption of neurotransmitter storage might mediate defective presynaptic release.

Original languageEnglish (US)
Pages (from-to)224-234
Number of pages11
JournalToxicological Sciences
Volume89
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

Corpus Striatum
Acrylamide
Synaptic Vesicles
Rats
Dopamine
Neurotransmitter Agents
Ethylmaleimide
Iodoacetic Acid
Nerve Degeneration
Sulfhydryl Reagents
Synaptosomes
Silver
Glutathione
Coloring Agents
Membranes
Kinetics

Keywords

  • Acrylamide
  • Adduct formation
  • Nerve terminal
  • Neurotransmitter uptake
  • Synaptic vesicles
  • Toxic axonopathy

ASJC Scopus subject areas

  • Toxicology

Cite this

Acrylamide inhibits dopamine uptake in rat striatal synaptic vesicles. / LoPachin, Richard M.; Barber, David S.; He, Deke; Das, Soma.

In: Toxicological Sciences, Vol. 89, No. 1, 01.2006, p. 224-234.

Research output: Contribution to journalArticle

LoPachin, Richard M. ; Barber, David S. ; He, Deke ; Das, Soma. / Acrylamide inhibits dopamine uptake in rat striatal synaptic vesicles. In: Toxicological Sciences. 2006 ; Vol. 89, No. 1. pp. 224-234.
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