Current evidence supports the hypothesis that somatostatin-related peptides contained within the central nervous system (CNS) participate in the regulation of epinephrine secretion from the adrenal medulla. Proposed in this grant application are the studies necessary to critically test this hypothesis. Somatostatin-28 (SS-28) will be microinjected into different brain parenchymal regions of awake rats to determine the CNS site of action of this peptide to inhibit adrenal epinephrine secretion. Once a site(s) of action of SS-28 has been characterized a somatostatin-receptor antagonist will be microinjected into this site to determine the effects of blocking the actions of endogenous somatostatins on adrenal epinephrine secretion. The CNS neuroanatomy of somatostatin-containing nerve fibers and cell bodies and their relationship to the CNS site of action of SS-28 will be assessed using combined immunohistochemical and retrograde transport methods. Knowledge of the location of aomatostatin-containing cell bodies projecting to the site of action of SS-28 will provide the basis for experiments in which these cell bodies or their porjections are depleted of peptide or destroyed. These experiments, in addition to the somatostatin antagonist experiments, will provide information on the physiologic importance of endogenous somatostatin related peptides in the regulation of the adrenal medulla. Further support for this hypothesis will be sought by investigating somatostatin turnover in brain areas identified to be important in the regulation of adrenal epinephrine secretions. Physiologic models for the study of adrenal epinephrine secretion will include insulin-induced hypoglycemis, cold exposure, exercise, glucose administration and volume expansion by administration of whole blood.
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