The objective of the research is to identify chemically the presumptive peripheral transmitter(s) of the cochlear nucleus of the guinea pig, the lateral-line organ of Xenopus laevis (the African clawed frog), and of labyrinthine organs of fish, and to characterize the biochemical systems associated with the presumptive transmitter(s). Analytical methods include: 1) high-resolution, high-performance liquid chromatography (HPLC) with fluorescence detection and detection by radioactivity, 2) mass spectrometry, for confirmation of chemical composition of HPLC fractions, 3) radioligand-receptor binding assays and autoradiographic localization, for characterization of neurotransmitter receptors of acoustico-lateralis fractions, 4) fluorometric and radioisotopic assays, for determination of transmitter-related enzymes of hair-cell fractions, and 5) a bioassay using the Xenopus lateral line, for detecting transmitter-like activity. Preparative methods include: 1) a surgical approach to the guinea-pig cochlea and temporal bone, for collection of perilymph and cerebrospinal fluid from guinea pigs in the presence and absence of noise, before determining small-molecule content of the fluids, 2) an in vitro system for release of presumptive neurotransmitters from acoustico-lateralis tissues, and 3) dissection of Xenopus lateral line, fish labyrinthine, and guinea-pig auditory fractions, prior to determination of their small-molecule content, enzyme activity, and receptor content. Using these methods, we plan to establish the identity, and presence in the lateral-line neuromast and fish labyrinthine organs, of presumptive acoustico-lateral-is transmitter(s), its (their) associated receptors and synthesizing and degrading enzymes, and its (their) biological activity. We also plan to establish the identity, stimulated release into perilymph, and biological activity of presumptive guinea-pig cochlear transmitter(s). We further plan to identify chemically non-transmitter materials that are releasted into perilymph during exposure of guinea pigs to noise at high levels. This predominantly biochemical approach should lead to the identification of peripheral neurotransmitter(s) of hearing and balance, and will suggest eventual therapies for transmitter-related hearing loss, tinnitus, and dizziness.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Hearing Research Study Section (HAR)
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Wayne State University
Schools of Medicine
United States
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Guth, S L; Drescher, D G (1990) Effects of divalent cations on the frequency of spontaneous action potentials from the lateral line organ of Xenopus laevis. Brain Res 508:76-84
Khan, K M; Drescher, D G (1990) Proteins of the gelatinous layer of the trout saccular otolithic membrane. Hear Res 43:149-58
Drescher, D G; Khan, K M; Arden, R L et al. (1989) Protein associated with the sensory cell layer of the rainbow trout saccular macula. Brain Res 485:225-35
Drescher, D G; Drescher, M J (1987) Spontaneous neural activity of a mechanoreceptive system is undiminished by replacement of external calcium with equimolar magnesium in the presence of EGTA. Life Sci 40:1371-7
Drescher, D G; Drescher, M J (1987) Calcium and magnesium dependence of spontaneous and evoked afferent neural activity in the lateral-line organ of Xenopus laevis. Comp Biochem Physiol A Comp Physiol 87:305-10
Drescher, M J; Drescher, D G (1987) Amino acids, including neurotransmitter candidates, in a hair cell-enriched fraction from the lateral line of Xenopus laevis. Comp Biochem Physiol A Comp Physiol 86:553-8
Drescher, M J; Drescher, D G; Hatfield, J S (1987) Potassium-evoked release of endogenous primary amine-containing compounds from the trout saccular macula and saccular nerve in vitro. Brain Res 417:39-50
Potter, A J; Drescher, M J; Drescher, D G (1986) Potassium-stimulated efflux of radiolabeled products formed from L-[14C(U)]-glutamine in vitro by the saccule of the rainbow trout (Salmo gairdnerii R.). Comp Biochem Physiol A Comp Physiol 84:265-70