Neurons located in the ventral medulla project to the thoracic intermediolateral cell column (IML) and modulate sympathetic activity to the cardiovascular system. Numerous putative neurotransmitters are found either alone or coexisting in cell bodies of IML-projecting ventral medullary neurons that are located in the midline raphe and paraphyramidal region. Substance P (SP), serotonin (5HT), and thyrotropin-releasing hormone (TRH) coexist in individual IML-projecting cells, Neurokinin A (NKA), another tachykinin peptide related to SP, may also be colocalized in these neurons. We propose that each of these colocalized neurochemical agents is released in the IML and affects the cardiovascular system either directly through interactions with IML neurons or indirectly by modifying the effects of another colocalized agent. To test this, we will: (1) obtain additional information on the chemical neuroanatomy of these 4 coexisting putative transmitter systems in IML-projecting ventral medullary neurons; (2) determine which of the colocalized neurochemical on their release; (3) asses the influence of the multiple colocalized putative transmitters and their interactions on cardiovascular control. The techniques to be used in these studies include: multiple fluorescence labeling of single cells with immunocytochemistry and retrograde tracers, in vitro receptor autoradiography, both in vitro and in vivo studies of the release of putative transmitters, and in vivo pharmacologic and hemodynamic studies in rats. These studies will provide information on the neurochemical and functional significance of the presence of multiple putative transmitters in IML- projecting neurons and provide insights into a possible neurochemical basis for discrete modulation and ultimately therapeutic manipulation of sympathetic input to the cardiovascular system. In addition, the information will provide more general insights into the neurobiology of colocalized neurochemical.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024876-07
Application #
3409856
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1986-08-01
Project End
1995-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Henry M. Jackson Fdn for the Adv Mil/Med
Department
Type
DUNS #
City
Rockville
State
MD
Country
United States
Zip Code
20817
Helke, C J; Capuano, S; Tran, N et al. (1997) Immunocytochemical studies of the 5-HT(1A) receptor in ventral medullaryneurons that project to the intermediolateral cell column and contain serotonin or tyrosine hydroxylase immunoreactivity. J Comp Neurol 379:261-70
Routh, V H; Helke, C J (1997) A novel technique for producing antibody-coated microprobes using a thiol-terminal silane and a heterobifunctional crosslinker. J Neurosci Methods 71:163-8
Yang, L; Thomas, N D; Helke, C J (1996) Characterization of substance P release from the intermediate area of rat thoracic spinal cord. Synapse 23:265-73
Nevin, K; Zhuo, H; Helke, C J (1994) Neurokinin A coexists with substance P and serotonin in ventral medullary spinally projecting neurons of the rat. Peptides 15:1003-11
Yang, L; Jacocks 3rd, H M; Helke, C J (1994) Release of [3H]5-hydroxytryptamine from the intermediate area of rat thoracic spinal cord is modulated by presynaptic autoreceptors. Synapse 18:198-204
Helke, C J; McDonald, C H; Phillips, E T (1993) Hypotensive effects of 5-HT1A receptor activation: ventral medullary sites and mechanisms of action in the rat. J Auton Nerv Syst 42:177-88
Thor, K B; Nickolaus, S; Helke, C J (1993) Autoradiographic localization of 5-hydroxytryptamine1A, 5-hydroxytryptamine1B and 5-hydroxytryptamine1C/2 binding sites in the rat spinal cord. Neuroscience 55:235-52
Zhuo, H; Helke, C J (1993) Neurokinin B peptide-2 neurons project from the hypothalamus to the thoracolumbar spinal cord of the rat. Neuroscience 52:1019-28
Thor, K B; Blitz-Siebert, A; Helke, C J (1992) Autoradiographic localization of 5HT1 binding sites in autonomic areas of the rat dorsomedial medulla oblongata. Synapse 10:217-27
Thor, K B; Blitz-Siebert, A; Helke, C J (1992) Autoradiographic localization of 5HT1 binding sites in the medulla oblongata of the rat. Synapse 10:185-205

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