| People - Faculty - Professor: Stanley M. Parsons
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| Field(s): |
Biological
Chemistry |
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| Email: |
parsons@chem.ucsb.edu |
| Phone: |
(805) 893- 2252
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Fax: (805) 893- 4120 |
| Office: |
1126B Chem
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Selected Publications |
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Go to Research
Group website |
| Bio: |
Dr. Parsons received his
Ph.D. at the California Institute of Technology in 1971. After
postdoctoral study at UC Berkeley, he came to UCSB in 1972. Dr. Parsons
is a Javits Neuroscience Investigator and an editor of the "Journal of
Neurochemistry". |
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Current
Research
My group is studying
storage of the neurotransmitter acetylcholine (ACh) by synaptic
vesicles, which are hollow storage organelles located in nerve
terminals. When a nerve impulse arrives at the terminal, it causes
synaptic vesicles to secrete ACh into the synaptic gap where it acts to
propagate the signal to the next cell. Synaptic vesicles are used many
times, so they must be refilled between nerve impulses. Refilling is
mediated by a transporter called the vesicular ACh transporter (VAChT).
VAChT resides in the vesicular membrane and exchanges one ACh molecule
from cytoplasm for two vesicular protons that are supplied by a
separate proton pump. ACh inside synaptic vesicles is 100-fold
concentrated compared to ACh in the cytoplasm. VAChT is potently
inhibited by a drug called vesamicol, which acts at an allosteric site.
We are characterizing structure-function in VAChT with the long term
aim of learning how to stimulate ACh storage pharmacologically. We have
developed a microscopic kinetics model that describes individual steps
in the overall transport cycle. Our experiments involve expression of
cloned VAChT in a mammalian cell line called PC12. The cDNA for VAChT
is mutated to change potentially interesting amino acid residues, and
mutated VAChT located in vesicles is isolated from PC12 cells. The
preparation is characterized as to ACh and vesamicol binding
affinities, Km and Vmax values for ACh transport, and the pH
dependencies of all parameters. Partial identification of binding sites
for ACh, vesamicol and protons has been achieved. Also, important sites
of flexibility in the polypeptide backbone that control rates of
conformational change during transport have been identified.
Our long term goal is to understand how the VAChT works and is
regulated. The information might present an opportunity to increase ACh
storage in and subsequent release from distressed nerve terminals, such
as occurs in Alzheimer's and other diseases.
In other work involving a collaboration with Professor David Harris, we
are developing rapid and inexpensive tests for the compound
gamma-hydroxybutyrate (GHB). GHB produces sedation and a trance-like
state with loss of memory. Because it has little smell or taste, it can
be ingested unknowingly. This combination of properties has made GHB a
"date rape" drug that often is administered to victims in beverages.
Current assays for GHB either require sophisticated equipment, a
skilled person and a long time period to complete, or they use
chemistry that is hazardous, multi-step, insensitive and very
susceptible to false positives. We have developed an enzymatic test
that uses cloned GHB dehydrogenase. Oxidation of GHB is coupled to the
reduction of a pro-dye that yields a highly colored product in seconds.
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| Selected
Research Publications |
Reliable,
sensitive, rapid and quantitative enzyme-based assay for
gamma-hydroxybutyric acid (GHB). Bravo, D. T., Harris, D. O.,
and Parsons,
S. M. (2004) J. Forensic Sci. 49, 1-9. See Chem. & Eng.
News 81 (48), 36
(2003) and Anal. Chem. 76, 118A (2004) for commentaries. |
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Transmembrane
reorientation of the substrate binding site in vesicular
acetylcholine transporter. Bravo, D. T., Kolmakova, N. G.,
and Parsons, S.
M. (2004) Biochemistry 43, 8787-8793.
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Acetylcholine
binding site in the vesicular acetylcholine transporter.
Ojeda, A. M., Kolmakova, N. G. and Parsons, S. M. (2004) Biochemistry
43,
11163-11174.
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Choline
is transported by vesicular acetylcholine transporter. Bravo,
D.
T., Kolmakova, N. G. and Parsons, S. M. (2004) J. Neurochem.
91, 766-768.
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"Membrane
Transporters. Receptor Biochemistry and Methodology,"
edited by
M. W. Quick. Hoboken (New Jersey): Wiley-Liss, c2002, xiii,
291 p. (Book
Review)." Parsons, S. M. (2004) Quarterly Review of Biology
79.1, 70.
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Synthesis
and in vitro evaluation of new benzovesamicol analogues as
potential imaging probes for the vesicular acetylcholine transporter.
Zea-Ponce, Y., Mavel, S., Assaad, T., Kruse, S. E., Parsons,
S. M., Emond,
P., Chalon, S., Giboureau, N., Kassiou, M., and Guilloteau,
D. (2005)
Bioorganic & Medicinal Chemistry 13, 745-753.
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Mutational
and pH analysis of ionic residues in transmembrane domains
of
vesicular acetylcholine transporter. Bravo, D. T., Kolmakova,
N. G., and
Parsons, S. M. (2005) Biochemistry 44, 7955-7966.
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Structural
requirements for steady-state localization of the vesicular
acetylcholine transporter in a cholinergic cell line. Ferreira,
L. T.,
Santos, M. S., Kolmakova, N. G., Koenen, J., Barbosa Jr.,
J., Gomez, M. V.,
Guatimosim, C., Zhang, X., Parsons, S. M., Prado, V. F. and
Prado, M. A. M.
(2005) J. Neurochem. 94, 957-969.
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New
transport assay demonstrates vesicular acetylcholine transporter
has
many alternative substrates. Bravo, D. T., Kolmakova, N. G.,
and Parsons,
S. M. (2005) Neurochem. Intern. 47, 243-247.
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Synthesis
and in vitro evaluation of N-substituted aza-trozamicol analogs
as vesicular acetylcholine transporter ligands. Assaad, T.,
Mavel, S.,
Parsons, S. M. Kruse, S., Galineau, L., Allouchi, H., Kassiou,
M., Chalon,
S., Guilloteau, D., and Emond. P. (2006) Bioorg. Med. Chem.
Lett. 16,
2654-2657.
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Mutational
and bioinformatics analysis of proline- and glycine-rich motifs
in vesicular acetylcholine transporter. Chandrasekaran, A.,
Ojeda, A. M.,
Kolmakova, N. G., and Parsons, S. M. (2006) J. Neurochem.
98, 1551-1559.
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