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.
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