Transporter maintenance of dopamine homeostasis

  • Wilhelm, Clare, (PI)

Project: Research project

Description

DESCRIPTION (provided by applicant): The dopamine (DA) transporter (DAT) is the primary mechanism for removing dopamine from the synaptic cleft. Once taken up by the DAT, DA can be either degraded enzymatically, or recycled and repackaged into vesicles by the vesicular monoamine transporter (VMAT2). It is the synergistic interaction of these two proteins, DAT and VMAT2, that lead to DA homeostasis in dopaminergic neurons. Improper function or expression of either of these proteins results in altered homeostasis and has been associated with many clinical pathologies, including depression and Parkinson's disease. Of particular interest is regulation due to substance abuse, since the DAT is a primary site of action of psychostimulants such as cocaine and amphetamine. Therefore, the goals of this proposal are to examine how DAT and VMAT2, co-expressed in immortalized cell lines, interact to maintain homeostasis, and how their function and regulation is altered by drugs of abuse. The specific aims of this proposal are to: 1) characterize the effect of co-expression of these two proteins on DA homeostasis in a cell system, 2) examine the effect co-expression on drug-induced neurotransmitter regulation, and 3) determine the effect of co-expression on drug-induced reactive oxygen species formation.
StatusFinished
Effective start/end date8/24/048/23/06

Funding

  • National Institutes of Health: $34,140.00
  • National Institutes of Health: $20,203.00

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Dopamine Plasma Membrane Transport Proteins
Homeostasis
Maintenance
Dopamine
Vesicular Monoamine Transport Proteins
Proteins
Clinical Pathology
Dopaminergic Neurons
Street Drugs
Amphetamine
Cocaine
Pharmaceutical Preparations
Substance-Related Disorders
Neurotransmitter Agents
Parkinson Disease
Reactive Oxygen Species
Depression
Cell Line

ASJC

  • Medicine(all)