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.
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