Olfactory communication has received considerable attention during the last decade. While much new information has been gained from the biochemIcal and electrophysiological investigations of the olfactory epithelium, the key biomolecules (olfactorily active proteins) remain insufficiently characterized. The recent availability of specific odorants, loosely referred to as """"""""pheromones"""""""" or """"""""semiochemicals"""""""" in our laboratory provides a unique opportunity to probe the olfactory proteins and related biomolecules. Several odorants with a specific endocrinological and/or behavioral response in the house mouse (Mus domesticus) will be used in the proposed studies. Binding of isotopically labeled pheromones with the olfactory receptor proteins will be employed to isolate such biomolecules from samples of the mouse olfactory cilia by a set of chromatographic and electrophoretic techniques. Novel bioanalytical techniques (miniaturized liquid chromatography, laser induced fluorescence detection and electrospray mass spectrometry will be employed to characterize minute quantities of such proteins. Similarly, the odorant-binding protein of the nasal mucus will be characterized in relation to these pheromones. The measurements of binding constants and the extent of adenylate cyclase stimulation will be conducted for the sets of male and female pheromones and the olfactory proteins isolated from animals of different sex, endocrine status, and behavioral experience. The recently crystallized bovine pyrazine-binding protein will provide an additional model system to study the molecular aspects of ligand-protein interactions, including the stereospecific binding with dehydro-exo-brevicomin (a proven male mouse pheromone with optical activity). Odorant-binding studies will also be extended to the vomeronasal organ, another olfactorily responsive entity in rodents. While the proposed research is designed to elucidate certain aspects of olfaction in rodents, new insights into the molecular mechanisms involved are pertinent to a better understanding of human olfaction and its physiology.
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