The proposed project consists of 3 independent investigations designed to study different aspects of somatostatin. The first objective is to investigate whether somatostatin has physiologically significant hormonal actions. Specifically, we plan to determine the peripheral SLI concentrations necessary to suppress release of gastro-entero-pancreatic (GEP) hormones (gastrin, glucagon, pancreatic polypeptide), a pituitary hormone (growth hormone), exocrine, gastric, and pancreatic secretions (gastric acid and pancreatic bicarbonate and enzyme secretion) and gastro-intestinal motility. The second objective is to study neural control of somatostatin release. Specifically, we plan to study the effect of adrenergic, cholinergic, serotoninergic and dopaminergic agents and of electrical stimulation of the vagal and splanchnic nerves on somatostatin release. The third objective is to study the metabolism of somatostatin. Specifically, we plan to measure arterial-venous concentration differences of somatostatin across several organs including liver, kidney, brain, and muscle. In addition, we will determine the half life of dissapearance, metabolic clearance rate, and volume of distribution of exogenously administered somatostatin. Lastly, we will investigate possible somatostatin degrading effects of plasma. All experiments will be performed in dogs. Somatostatin will be measured in plasma using a sensitive, specific and reproducible radioimmunoassay.
