The hypothesis upon which this competitive renewal application is bases states that neuropeptides play a role in homeostatic regulatory mechanisms in the human, and that aberrations in those neuropeptidergic pathways exist in a variety of pathophysiological conditions. We propose to identify and quantify peptides produced by the opioid (proenkephalins A and B, proopiomelanocortin=POMC) and tachykinin pathways in human tissues and fluids. The use of a combination of powerful state-of-the-art analytical methodologies (RP-HPLC, RIA, RRA, FAB-MS-MS) that maximize both the detection sensitivity and molecular specificity in the study of human pathophysiological conditions is a unique aspect of our proposed research. To test experimentally our hypothesis, we propose to: 1. acquire human tissues and fluids rapidly and treat those samples to minimize metabolic interconversions; 2. measure the levels of individual peptides in control versus the stressed and pathophysiological conditions; 3. determine the primary structure of the measured peptide in order to be able to identify the endogenous peptides with a high degree of molecular specificity, and; 4. measure the levels of peptide precursors of the individual peptides through the use of enzyme and chemical techniques followed by subsequent measurement of the excised peptide.
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