In this project we will use neuroanatomical, electrophysiological and pharmacological techniques to examine the sympathetic and parasympathetic reflex mechanisms involved in the neural control of urinary bladder and large intestine of the cat. The project will focus on two major areas: (1) the mechanisms underlying transmission in vesical and colonic parasympathetic ganglia and (2) the organization of the lumbar sympathetic outflow to the bladder and intestine, including afferent pathways, as well as the spinal interneuronal and preganglionic neuronal systems. Specific topics to be explored are: (1) the identification of peptide neurotransmitters in peripheral ganglia and visceral primary afferent systems, (2) the role of inhibitory and facilitatory mechanisms in modulating transmission in peripheral ganglia, (3) plasticity in ganglionic pathways following neural damage, (4) the morphology of autonomic ganglion cells and their synaptic inputs, (5) the central projections of visceral primary afferents at the thoracolumbar level, and (6) the identification in the lumbar spinal cord of interneuronal and preganglionic cell groups involved in excretory reflexes. The ultimate objectives in this investigation are to provide a wiring diagram for lumbar sympathetic pathways which control micturition and defecation, and to provide a more complete description of the central and peripheral ganglionic mechanisms that integrate the sympathetic and parasympathetic inputs to the excretory organs. It is anticipated that this research will provide further insight into the function of peptides in the nervous system, and the organization visceral afferent and spinal interneuronal mechanisms; two areas that have received relatively little attention. The study of lumbar sympathetic pathways has considerable clinical relevance since it is now recognized that abnormal sympathetic nervous activity may contribute to disorders of excretory function, particularly in the lower urinary tract. Thus, it seems reasonable to expect that the information to be gained in the proposed experiments about central reflex mechanisms and the identity of neurotransmitters in the lumbar sympathetic pathways will lead to more effective diagnoses and pharmacological treatment of urinary and intestinal dysfunction.

Project Start
1983-06-01
Project End
1986-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
de Groat, W C (1990) Central neural control of the lower urinary tract. Ciba Found Symp 151:27-44;discussion 44-56
Steers, W D; Mackway, A M; Ciambotti, J et al. (1990) Effects of streptozotocin-induced diabetes on bladder function in the rat. J Urol 143:1032-6
Somogyi, G T; de Groat, W C (1990) Modulation of the release of [3H]norepinephrine from the base and body of the rat urinary bladder by endogenous adrenergic and cholinergic mechanisms. J Pharmacol Exp Ther 255:204-10
Steers, W D; Ciambotti, J; Erdman, S et al. (1990) Morphological plasticity in efferent pathways to the urinary bladder of the rat following urethral obstruction. J Neurosci 10:1943-51
Theobald Jr, R J; de Groat, W D (1989) The effects of purine nucleotides on transmission in vesical parasympathetic ganglia of the cat. J Auton Pharmacol 9:167-81
Noto, H; Roppolo, J R; Steers, W D et al. (1989) Excitatory and inhibitory influences on bladder activity elicited by electrical stimulation in the pontine micturition center in the rat. Brain Res 492:99-115
Keast, J R; Booth, A M; de Groat, W C (1989) Distribution of neurons in the major pelvic ganglion of the rat which supply the bladder, colon or penis. Cell Tissue Res 256:105-12
Steers, W D; De Groat, W C (1988) Effect of bladder outlet obstruction on micturition reflex pathways in the rat. J Urol 140:864-71
Kawatani, M; Rutigliano, M J; de Groat, W C (1987) Vasoactive intestinal polypeptide facilitates the late component of the 5-hydroxytryptamine-induced discharge in the cat superior cervical ganglion. Neurosci Lett 73:59-64
Rutigliano, M J; Kawatani, M; De Groat, W C (1986) Vasoactive intestinal polypeptide elicits a discharge in chronically decentralized sympathetic ganglia. Eur J Pharmacol 129:375-8

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