One of the more unexpected findings in brain-gut peptide physiology has been that many of these peptides have dramatic effects on sympathetic nervous system function when introduced into the brain. This has been most widely investigated in terms of the rapid and pronounced hyperglycemia many of these agents produce. Since most of these studies have been done using intraventricular or intracisternal injections into the brain, the exact active sites of these materials are unknown. Also undetermined are the efferent pathways and """"""""downstream"""""""" nuclei which are important in mediating the effects of these peptides. The experiments described here are tightly focused on two closely interrelated questions: 1) what are the active sites of three peptides (bombesin, corticotropin releasing factor [CRF], somatostatin) which are known to affect glucoregulation; 2) what further regions and specific areas do these active sites stimulate in turn. These questions will be addressed by a combination of 1) microinfusion mapping of the brain for the active sites of these peptides; and 2) transection of the output pathways from identified active sites. The major dependent variable will be serum glucose. Determination of reliable effects on this measure will be followed by a more general appraisal of sympathetic function at selected active sites, including measurement of serum free fatty acids, glucagon, adrenocorticotropic hormone, and catecholamine levels. These studies will provide significant new knowledge about the role of peptides in the central control of circulating glucose by the sympathetic nervous system, including sites of action and efferent pathways. Additionally, these studies will provide further insights into the basic organization and localization of the control of sympathetic function in the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020660-02
Application #
3401181
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1985-09-30
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Steinman, J L; Gunion, M W; Morley, J E (1994) Forebrain and hindbrain involvement of neuropeptide Y in ingestive behaviors of rats. Pharmacol Biochem Behav 47:207-14
Walford, R L; Harris, S B; Gunion, M W (1992) The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans. Proc Natl Acad Sci U S A 89:11533-7
Babcock, A M; Barton, C; Gunion, M W et al. (1992) Bombesin-induced hypothermia and hypophagia are associated with plasma metabolic fuel alterations in the rat. Physiol Behav 51:933-8
Gunion, M W; Rosenthal, M J; Miller, S et al. (1992) Role of hypothalamic paraventricular nucleus alpha- and beta-adrenergic receptors in regulation of blood glucose, free fatty acids and corticosterone. Brain Res 588:84-96
Gunion, M W; Grijalva, C V; Tache, Y et al. (1991) Destruction of different fiber tracts underlies development of lateral hypothalamic lesion-induced hyperthermia and loss of bombesin-induced hypothermia. Brain Res 560:326-9
Gunion, M W; Rosenthal, M J; Morley, J E et al. (1991) mu-receptor mediates elevated glucose and corticosterone after third ventricle injection of opioid peptides. Am J Physiol 261:R70-81
Gunion, M W; Rosenthal, M J; Tatemoto, K et al. (1989) Intracranial microinfusion of pancreastatin elevates blood glucose, free fatty acids, and corticosterone in rats. Brain Res 485:251-7
Gunion, M W; Tache, Y; Rosenthal, M J et al. (1989) Bombesin microinfusion into the rat hypothalamic paraventricular nucleus increases blood glucose, free fatty acids and corticosterone. Brain Res 478:47-58
Gunion, M W; Rosenthal, M J; Tache, Y et al. (1988) Intrahypothalamic microinfusion of corticotropin-releasing factor elevates blood glucose and free fatty acids in rats. J Auton Nerv Syst 24:87-95
Gunion, M W; Tache, Y (1987) Intrahypothalamic microinfusion of corticotropin-releasing factor inhibits gastric acid secretion but increases secretion volume in rats. Brain Res 411:156-61

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