Disturbances in the regulation of blood pressure may result from perturbations of transmitter mechanisms in the nucleus tractus solitarius (NTS), the site of termination of primary cardiovascular afferents. Thus, definition of the role played by putative transmitters in the NTS may increase understanding of central control of blood pressure. The principal investigator had previously shown that glycine (GLY) is released in the NTS. Micorinjection of the amino acid into the dorsal NTS elicits a depressor and bradycardiac response that is qualitatively like that of the excitatory amino acid glutamate (GLU), while injections into the ventral NTS and dorsal motor nucleus of the vagus (DMV) result in pressor, tachycardiac responses. Studies from the investigator's laboratory have supported a role for ACh, and have not supported glycine-glutamate receptor interactions in the mediation of these cardiovascular responses. The investigator will test the hypothesis that GLY elicits cardiovascular responses from the NTS through cholinergic mechanisms and specifically through the release of ACh. The role of GLY in the NTS in cardiovascular reflexes will be tested and projections from the functionally different sites in the NTS will be determined. The role of ACh in mediating the responses to GLY will be assessed and the mechanisms by which GLY leads to ACh release will be determined. Immunocytochemical methods will be used to identify and localize GLY-containing terminals and GLY receptors, and the relationship of those GLY elements to cholinergic neurons and nerve processes will be investigated. Finally, the relationship between GLY terminals and cardiovascular afferent fibers will be investigated to determine if GLY may be released from primary afferents or from interneurons within the NTS.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032205-07
Application #
2216976
Study Section
Neurology A Study Section (NEUA)
Project Start
1991-02-01
Project End
1996-01-31
Budget Start
1994-02-01
Budget End
1995-01-31
Support Year
7
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Iowa
Department
Neurology
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
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Cassell, M D; Yi, H; Talman, W T (2000) Glycine receptor (gephyrin) immunoreactivity is present on cholinergic neurons in the dorsal vagal complex. Neuroscience 95:489-97
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Lin, L H; Cassell, M D; Sandra, A et al. (1998) Direct evidence for nitric oxide synthase in vagal afferents to the nucleus tractus solitarii. Neuroscience 84:549-58
Talman, W T (1997) The myth of nitric oxide in central cardiovascular control by the nucleus tractus solitarii. Braz J Med Biol Res 30:515-20
Talman, W T (1997) Nitroxidergic transmission in the nucleus tractus solitarii. Ann N Y Acad Sci 835:225-33
Talman, W T (1997) Glutamatergic transmission in the nucleus tractus solitarii: from server to peripherals in the cardiovascular information superhighway. Braz J Med Biol Res 30:1-7
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Lin, L H; Sandra, A; Boutelle, S et al. (1997) Up-regulation of nitric oxide synthase and its mRNA in vagal motor nuclei following axotomy in rat. Neurosci Lett 221:97-100

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