The primary goal of the studies proposed in this grant application is to determine the role of brain somatostatin in the regulation of pituitary vasopressin and adrenal epinephrine secretion. Somatostatin-28 (SS-28), placed into discrete brain regions, elevates plasma concentration of vasopressin and decreases plasma levels of epinephrine. Continuous infusion of SS-28 into the lateral cerebroventricle produces a significant depletion of vasopressin levels within the paraventricular nucleus of the hypothalamus as determined by immunocytochemistry. Depletion of brain somatostatin with cysteamine attenuates hemorrhage-induced elevation of plasma concentration of vasopressin. Somatostatin- like peptides (SLP) are present in brain regions which are involved in the regulation of pituitary vasopressin and adrenal epinephrine secretion. A systematic search for the sites of action of SS-28 to stimulate vasopressin and to inhibit epinephrine secretion and the relationship of these sites to the anatomic distribution of SLP within the central nervous system (CNS) is proposed. These objectives will be achieved by combining pharmacologic, physiologic and neuroanatomic methodologies. Based on our knowledge of neural pathways that regulate vasopressin and adrenal epinephrine secretion and on information on the CNS distribution of SLP, brain areas will be chosen for evaluation for sites of action of SS-28. Following the identification of these sites, analyses will te made for the presence and cellular origin of SLP contained in nerve terminals within this region. The role of specific SLP-containing pathways in the physiologic regulation of vasopressin secretion will be assessed using available tools to modify the release or action of endogenous SLP. Additional studies will assess the role of other characterized putative regulators of vasopressin secretion in mediating the actions of SS-28 These studies will increase our understanding of the role that specific brain SLP-containing pathways play in the regulation of pituitary vasopressin and adrenal epinephrine secretion.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL037716-07
Application #
3353659
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1986-05-01
Project End
1993-09-29
Budget Start
1991-09-30
Budget End
1992-09-29
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Hauger, R L; Irwin, M R; Lorang, M et al. (1993) High intracerebral levels of CRH result in CRH receptor downregulation in the amygdala and neuroimmune desensitization. Brain Res 616:283-92
De Nicola, L; Thomson, S C; Wead, L M et al. (1993) Arginine feeding modifies cyclosporine nephrotoxicity in rats. J Clin Invest 92:1859-65
Rivier, J; Rivier, C; Galyean, R et al. (1993) Single point D-substituted corticotropin-releasing factor analogues: effects on potency and physicochemical characteristics. J Med Chem 36:2851-9
Fisher, L; Rivier, C; Rivier, J et al. (1991) Differential antagonist activity of alpha-helical corticotropin-releasing factor9-41 in three bioassay systems. Endocrinology 129:1312-6
Carver-Moore, K; Gray, T S; Brown, M R (1991) Central nervous system site of action of bombesin to elevate plasma concentrations of catecholamines. Brain Res 541:225-31
Costello, J F; Brown, M R; Gray, T S (1991) Bombesin immunoreactive neurons in the hypothalamic paraventricular nucleus innervate the dorsal vagal complex in the rat. Brain Res 542:77-82
Allen, R; Boublik, J; Hauger, R L et al. (1991) Neuropeptide Y radio-immunoassay: characterization and application. Clin Exp Pharmacol Physiol 18:825-33
Lenz, H J; Brown, M R (1990) Cerebroventricular calcitonin gene-related peptide inhibits rat duodenal bicarbonate secretion by release of norepinephrine and vasopressin. J Clin Invest 85:25-32
Crum, R L; Dominic, W; Hansbrough, J F et al. (1990) Cardiovascular and neurohumoral responses following burn injury. Arch Surg 125:1065-9
Boublik, J; Scott, N; Taulane, J et al. (1989) Neuropeptide Y and neuropeptide Y18-36. Structural and biological characterization. Int J Pept Protein Res 33:11-5

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