The presence of acidic substances in the mouth evokes a sensation of sour taste. But oropharyngeal acidification is not only attributable to ingested substances, but may be produced by gastric reflux which evokes strong respiratory and salivary reflexes as well as a sensation of disgust. Acidic substances in the oral cavity not only trigger the taste system but also activate pH-sensitive general mucosal nerve fibers. Previous studies have identified the subset of taste cells necessary for sour transduction, but how these cells transmit the information to the gustatory nerves and thence the brainstem gustatory relay nuclei remains unclear. Acid-responsive mucosal nerve fibers also transmit information about intraoral pH and end within the brainstem in a partially overlapping fashion with the sour taste fibers. Experiments in this proposal utilize behavioral, pharmacological, anatomical and physiological means to examine to what degree the sour taste and non- taste systems contribute to the detection and avoidance of acids. The experiments rely on unique knockout rodent models to dissociate the functions and roles of the two intraoral acid-responsive systems. We will use both pharmacological and genetic tools to study what areas of the brainstem are activated by stimulation of one system in the absence of the other.
The sense of taste evolved to allow discrimination of nutritionally important compounds from toxic substances. The off-taste of a medicine can be a limiting factor in patient compliance. In addition, acid reflux evokes strong aversive respiratory and salivary reflexes due to the presence of acid in the oropharynx. A better understanding of the mechanisms used by oral acid sensors to detect noxious chemicals and transmit chemosensory information to the nervous system may lead to the development of pharmaceuticals that can limit the bad tastes of many drugs and ameliorate the negative hedonic aspects of reflux disease.
