Article

Expression and function of the rat vesicular monoamine transporter 2

Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
AJP Cell Physiology (Impact Factor: 3.67). 05/2008; 294(4):C1004-11. DOI: 10.1152/ajpcell.00348.2007
Source: PubMed

ABSTRACT The vesicular monoamine transporters (VMATs) are essential proteins, involved in the storage of monoamines in the central nervous system and in endocrine cells, in a process that involves exchange of 2H(+) with one substrate molecule. The VMATs interact with various native substrates and clinically relevant drugs and display the pharmacological profile of multidrug transporters. Vesicular transporters suffer from a lack of biochemical and structural data due to the difficulties in their expression. In this work we present the high-level expression of rat VMAT2 (rVMAT2) in a stable a human embryonic kidney cell line (HEK293), generated using the resistance to the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) conferred by the protein. In addition, we describe novel procedures for the solubilization and purification of active protein, and its reconstitution into proteoliposomes. The partially purified protein in detergent binds the inhibitor tetrabenazine and, after reconstitution, displays high levels of Deltamu(H+)-driven electrogenic transport of serotonin. The reconstituted purified rVMAT2 has wild-type affinity for serotonin, and its turnover rate is approximately 0.4 substrate molecule/s.

0 Followers
 · 
47 Views
  • Source
    • "The vesicular monoamine transporter 2 (VMAT2) located on the membrane of vesicles is responsible for storing and packaging neurotransmitters into monoamine vesicles or granules. Imaging VMAT2 in the brain provides a measurement reflecting the integrity of dopaminergic, noradrenergic and serotonergic neurons [304]. Positron emission tomography (PET) ligands for the VMAT2 have become valuable diagnostic tools. "
  • Source
    • "The vesicular monoamine transporter 2 (VMAT2) located on the membrane of vesicles is responsible for storing and packaging neurotransmitters into monoamine vesicles or granules. Imaging VMAT2 in the brain provides a measurement reflecting the integrity of dopaminergic, noradrenergic and serotonergic neurons [304]. Positron emission tomography (PET) ligands for the VMAT2 have become valuable diagnostic tools. "
  • Source
    • "The vesicular monoamine transporter 2 (VMAT2) located on the membrane of vesicles is responsible for storing and packaging neurotransmitters into monoamine vesicles or granules. Imaging VMAT2 in the brain provides a measurement reflecting the integrity of dopaminergic, noradrenergic and serotonergic neurons [304]. Positron emission tomography (PET) ligands for the VMAT2 have become valuable diagnostic tools. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cognitive enhancers (nootropics) are drugs to treat cognition deficits in patients suffering from Alzheimer's disease, schizophrenia, stroke, attention deficit hyperactivity disorder, or aging. Cognition refers to a capacity for information processing, applying knowledge, and changing preferences. It involves memory, attention, executive functions, perception, language, and psychomotor functions. The term nootropics was coined in 1972 when memory enhancing properties of piracetam were observed in clinical trials. In the meantime, hundreds of drugs have been evaluated in clinical trials or in preclinical experiments. To classify the compounds, a concept is proposed assigning drugs to 19 categories according to their mechanism(s) of action, in particular drugs interacting with receptors, enzymes, ion channels, nerve growth factors, re-uptake transporters, antioxidants, metal chelators, and disease modifying drugs, meaning small molecules, vaccines, and monoclonal antibodies interacting with amyloid-β and tau. For drugs, whose mechanism of action is not known, they are either classified according to structure, e.g., peptides, or their origin, e.g., natural products. The review covers the evolution of research in this field over the last 25 years.
    Journal of Alzheimer's disease: JAD 11/2012; 34(1). DOI:10.3233/JAD-121729 · 4.15 Impact Factor
Show more