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The glutamatergic receptors play a pivotal role in the brains neuronal
transmission. These receptors can be divided into two classes: 1) ionotropic
and 2) metabotropic. The NMDA ionotropic receptor is a tetrameric or pentameric
heteromeric complex that utilizes glutamate as a gatekeeper to control calcium
influx. The metabotropic receptor is a single polypeptide that uses glutamate
to stimulate signal transduction through G protein mediated pathways such
as phospholipase C. The NMDA and metabotropic receptors are thought to be
important in learning and memory. Both receptors have also been demonstrated
to have important roles in the underlying strengthening of neuronal transmission
in the hippocampus known as long term potentiation. Acute and chronic treatments
with ethanol have effects on the NMDA receptor. Fetal exposure to ethanol
has been suggested to have effects on NMDA and metabotropic receptors. Since
these glutamatergic receptors are important in learning and memory and are
impacted by exposure to ethanol, an understanding of these receptors may
be important in the pathology of alcoholism.
Research in my laboratory currently involves studies in how both NMDA and
metabotropic receptor classes participate in the acute and chronic effects
of ethanol in the central nervous system. As there are no high affinity ligands
available for either of these receptor systems, my studies utilize specific
antibodies. The specificity of these antibodies can be used to determine
not only how many receptors are present but how the different receptor subunits
are associated, what is the stoichiometry of the receptor, and what is the
phosphorylation status of these receptors. Experiments from my laboratory
will help to define the role that glutamatergic receptors may play in alcoholism
as well as provide information about fundamental questions of the NMDA receptor
complex structure and metabotropic receptor signal transduction pathways.
Selected Publications:
- Mao D, Perry DC, Yasuda RP, Wolfe BB, Kellar KJ: The alpha4beta2alpha5 nicotinic cholinergic receptor in rat brain is
resistant to up-regulation by nicotine in vivo J Neurochem.
104:446-56, 2008
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Ortinski PI, Turner JR, Barberis A, Motamedi G, Yasuda
RP, Wolfe BB, Kellar KJ, Vicini S:
Deletion of the GABA(A) receptor alpha1 subunit increases tonic GABA(A)
receptor current: a role for GABA uptake transporters.
J Neurosci. 26:9323-31, 2006
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Lu C, Fu Z, Karavanov I, Yasuda RP, Wolfe BB, Buonanno A,
Vicini S:
NMDA
receptor subtypes at autaptic synapses of cerebellar granule neurons.
J Neurophysiol.
96:2282-94, 2006
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Mao D, Yasuda RP, Fan H,
Wolfe BB, Kellar KJ:
Heterogeneity of nicotinic cholinergic receptors in rat superior cervical
and nodose Ganglia.
Mol Pharmacol.
70:1693-9, 2006
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N'Gouemo P, Yasuda RP, Morad M:
Ethanol withdrawal is accompanied by downregulation of calcium channel alpha
1B subunit in rat inferior colliculus neurons.
Brain Res.
1108:216-20, 2006
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Marritt AM, Cox BC, Yasuda RP, McIntosh JM, Xiao Y, Wolfe
BB, Kellar KJ:
Nicotinic cholinergic receptors in the rat retina: simple and mixed
heteromeric subtypes.
Mol Pharmacol.
68:1656-68, 2005
-
Brown KM, Wrathall JR, Yasuda RP, Wolfe BB:
Glutamate receptor subunit expression after spinal cord injury in young
rats.
Brain Res Dev Brain Res. 152:61-8, 2004
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Hernandez SC, Vicini S, Xiao Y, Dávila-García MI, Yasuda
RP, Wolfe BB, Kellar KJ:
The nicotinic receptor in the rat pineal gland is an alpha3beta4 subtype.
Mol Pharmacol.
66:978-87, 2004
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Jarabek BR, Yasuda RP, Wolfe BB:
Regulation of proteins affecting NMDA receptor-induced excitotoxicity in a
Huntington's mouse model.
Brain.
127:505-16, 2004
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Akinshola BE, Yasuda RP, Peoples RW, Taylor RE:
Ethanol sensitivity of recombinant homomeric and heteromeric AMPA receptor
subunits expressed in Xenopus oocytes.
Alcohol Clin Exp Res. 27:1876-83, 2003
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Al-Hallaq RA, Jarabek BR, Fu Z, Vicini S, Wolfe BB,
Yasuda RP:
Association of NR3A with the N-methyl-D-aspartate receptor NR1 and NR2
subunits.
Mol Pharmacol. 62:1119-27, 2002
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Brown KM, Wrathall JR, Yasuda RP, Wolfe BB:
Quantitative measurement of glutamate receptor subunit protein expression in
the postnatal rat spinal cord.
Brain Res Dev Brain Res. 137:127-33, 2002
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Yeh J, Ferreira M, Ebert S, Yasuda RP, Kellar KJ, Wolfe
BB:
Axotomy and nerve growth factor regulate levels of neuronal nicotinic
acetylcholine receptor alpha3 subunit protein in the rat superior cervical
ganglion.
J Neurochem.
79:258-65, 2001
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Ferreira M, Ebert SN, Perry DC, Yasuda RP, Baker CM,
Dávila-García MI, Kellar KJ, Gillis RA:
Evidence of a functional alpha7-neuronal nicotinic receptor subtype located
on motoneurons of the dorsal motor nucleus of the vagus.
J Pharmacol Exp Ther. 296:260-9, 2001
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Al-Hallaq RA, Yasuda RP, Wolfe BB:
Enrichment of N-methyl-D-aspartate NR1 splice variants and synaptic proteins
in rat postsynaptic densities.
J Neurochem.
77:110-9, 2001
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Yeh JJ, Yasuda RP, Dávila-García MI, Xiao Y, Ebert S,
Gupta T, Kellar KJ, Wolfe BB:
Neuronal nicotinic acetylcholine receptor alpha3 subunit protein in rat
brain and sympathetic ganglion measured using a subunit-specific antibody:
regional and ontogenic expression.
J Neurochem.
77:336-46, 2001
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Grossman SD, Wolfe BB, Yasuda RP, Wrathall JR:
Changes in NMDA receptor subunit expression in response to contusive spinal
cord injury.
J Neurochem.
75:174-84, 2000
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Wang Y, TesFaye E, Yasuda RP, Mash DC, Armstrong DM,
Wolfe BB:
Effects of post-mortem delay on subunits of ionotropic glutamate receptors
in human brain.
Brain Res Mol Brain Res. 80:123-31, 2000
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Dunah AW, Wang Y, Yasuda RP, Kameyama K, Huganir RL,
Wolfe BB, Standaert DG.
Alterations in subunit expression, composition, and phosphorylation of
striatal N-methyl-D-aspartate glutamate receptors in a rat 6-hydroxydopamine
model of Parkinson's disease.
Mol Pharmacol.
57:342-52, 2000
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Rosebraugh CJ, Yasuda RP, Yasuda SU:
Quantification of human H1 histamine receptor mRNA from peripheral blood.
Pharmacotherapy.
20:191-8, 2000
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