The primary sensory cell of the inner ear (the hair cell) releases a neurotransmitter to excite auditory nerve fibers. The identification of this transmitter, which may not be one of the known neurotransmitters, is the goal of this project. We have purified, from hair cell tissue and from retina, a substance that can excite afferent nerve fibers innervating hair cells. This substance appears to be a potent, unstable, unknown excitatory amino acid with pharmacological activity similar to glutamate; however, it is clearly not glutamate or any other commonly studied substance. The goals are to identify the chemical structure of the excitatory substance, to analyze its distribution in hair cell organs and in the nervous system and to determine its role in hair cell organ function. In addition to the intrinsic intellectual importance of identifying the neurotransmitter released by hair cells, this work may have significant practical implications for otolaryngology and sh ould have widespread importance for areas of neurobiology beyond the auditory system. If it is possible to develop drugs with some specificity for vestibular fibers, a treatment for motion sickness and intractable vertigo would likely result. Judicious use of a drug with specificity for the auditory system might alleviate some forms of peripheral tinnitus. The excitatory amino acid we have isolated from hair cell tissue and from retina is a good candidate to be a neurotransmitter in other parts of the nervous system; we already know that it is concentrated in inner ear and in retina. If it is localized discretely within the nervous system, it will almost assuredly provide a means of selectively studying transmission and function of other regions of the nervous system.

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Marintchev, Assen; Edmonds, Katherine A; Marintcheva, Boriana et al. (2009) Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation. Cell 136:447-60
Frueh, Dominique P; Arthanari, Haribabu; Koglin, Alexander et al. (2009) A double TROSY hNCAnH experiment for efficient assignment of large and challenging proteins. J Am Chem Soc 131:12880-1
Frueh, Dominique P; Leed, Alison; Arthanari, Haribabu et al. (2009) Time-shared HSQC-NOESY for accurate distance constraints measured at high-field in (15)N-(13)C-ILV methyl labeled proteins. J Biomol NMR 45:311-8
Lentz, Margaret R; Westmoreland, Susan V; Lee, Vallent et al. (2008) Metabolic markers of neuronal injury correlate with SIV CNS disease severity and inoculum in the macaque model of neuroAIDS. Magn Reson Med 59:475-84
Hyberts, Sven G; Heffron, Gregory J; Tarragona, Nestor G et al. (2007) Ultrahigh-resolution (1)H-(13)C HSQC spectra of metabolite mixtures using nonlinear sampling and forward maximum entropy reconstruction. J Am Chem Soc 129:5108-16
Chen, Jingyang; Dupradeau, Francois-Yves; Case, David A et al. (2007) Nuclear magnetic resonance structural studies and molecular modeling of duplex DNA containing normal and 4'-oxidized abasic sites. Biochemistry 46:3096-107
Lentz, Margaret R; Kim, John P; Westmoreland, Susan V et al. (2005) Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain. Radiology 235:461-8
Kim, John P; Lentz, Margaret R; Westmoreland, Susan V et al. (2005) Relationships between astrogliosis and 1H MR spectroscopic measures of brain choline/creatine and myo-inositol/creatine in a primate model. AJNR Am J Neuroradiol 26:752-9
Peled, S; Cory, D G; Raymond, S A et al. (1999) Water diffusion, T(2), and compartmentation in frog sciatic nerve. Magn Reson Med 42:911-8
Mo, H; Dai, Y; Pochapsky, S S et al. (1999) 1H, 13C and 15N NMR assignments for a carbon monoxide generating metalloenzyme from Klebsiella pneumoniae. J Biomol NMR 14:287-8

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