This research proposal is a combined neurophysiological and morphological investigation of the structure of membrane receptors for tastants in primate taste buds. Thaumatin, monellin and miraculin are proteins that in small quantities have very potent, long lasting effects exclusively in man and certain closely related primates. Thaumatin and monellin on a molar basis are both 104-105 times as sweet as sucrose. As little as 0.1 mg of miraculin (which in itself does not taste sweet) can make acids taste as if sugar has been added. Because all available data indicate that the rhesus monkey's response to these proteins is similar to that of man, this animal will be the primary experimental model. In neurophysiological experiments, we shall study in whole nerve and single fiber of the chorda tympani proper and glossopharyngeal nerves the effects of thaumatin, monellin, and derivatives of thaumatin, both alone and in combination with other compounds. Polyclonal and monoclonal antibodies against thaumatin and monellin will be used to explore their mechanism of action on sweet taste. In addition, we shall study the mechanism of the miraculin effect by use of miraculin antibodies. Since these substances have no effect on the sweet taste of rats, this species will be used as control animals. Our goals are to determine the location of binding sites for these proteins, and to relate the binding capacity of the proteins to their sweetness as revealed by physiological and morphological studies. The data may also be useful in understanding the molecular basis of hypogeusia, dysgeusia, and ageusia in man. We feel that our laboratories through our access to rhesus monkeys, our long experience in this area of research, our advanced facilities, our close cooperation with the biochemists who first characterized thaumatin and miraculin and shared in the characterization of monellin, and still are the only supplier of these substances, as well as through our own expertise, offer a unique research opportunity to elucidate the sweet taste in man.
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