AGONISTS/ANTAGONISTS FOR CHARACTERIZING CHEMORECEPTORS

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The senses of taste and olfaction are intimately involved in food selection, identification digestion and metabolism, as well as in reproduction (olfaction) and the general awareness and appreciation of the environment. Loss or alteration in function of these senses can lead to a nutritional compromises and to a decrease in the quality of life. The overall goal of our work has been the understanding of these senses at the molecular level, so that therapies for deficiencies of these sense may be approached from knowledgeable and rational bases. The current research proposal emphasizes production of antagonists and agonist to qustatory and olfactory receptors, and the use of these in characterizing the receptor binding proteins. The techniques of biochemistry, neurophysiology, synthetic organic chemistry and cell culture are central to the integrated collaborative approaches used to address the aims of this work. Our experimental model, the catfish, I. punctatus, possesses unique and identifiable receptors for various chemostimualtrou amino acids. This model has proved invalualboej to understanding the fundamental mechanisms of taste and olfaction. The specific aims of this proposal seek to (1) identify novel agonist and antagonists to taste and olfactory receptors form three major molecular classes - amino acid analogy (including photoaffinity probes), monoclonal antibodies and lectins; (2) characterize these agonist. antagonists using neurophysiological and biochemical binding assays, defining their specificity, mode of action and inhibitory kinetic; and (3) utilize these parve in characterizing events in reception and transduction and in labeling and identifying receptor proteins after electrophoresis. These aims will be accomplished through a series of experimental procedures that emphasize multidisiplinary approach. Specificity, mode of action and type of inhibition are studied using both stimulatory effectiveness and cross-adaptation procedures in a neurophysiological assay and competitive binding in biochemical assays. The resultant characterized probes and competitive binding in biochemical assays. The resultant characterized probe are then used to define the receptors as to subcalsand selectivity. Future studies will emphasize use of these proves in purifying and localizing receptors proteins in situ-upon completion of this study, we will have produced the chemical probes necessity for receptor identification, purification and documentation, and have achieved a more complete understanding of the receptor mechanisms in taste and olfaction.