SALT TASTE TRANSDUCTION AND ITS HORMONAL REGULATION

拟议工作的最终目标是确定机制

The ultimate goal of the proposed work is to determine the mechanisms involved in the transduction of salts in the fungiform and circumvallate taste receptors cells and the regulation of salt transducing elements by the peptide hormones arginine vasopressin and atrial natriuretic peptide. Using an electrophysiological approach, we will address the following specific aims: 1. What are the mechanisms for transduction of salty taste stimuli in the fungiform and circumvallate taste receptor cells of hamsters? Sodium salt transduction in fungiform taste receptor cells occurs by Na influx through amiloride-sensitive Na channels, but there is also an amiloride- insensitive component that is not well understood. Circumvallate taste receptor cells also respond to Na salts, but their transduction mechanisms have not been determined. Using a combination of patch clamp recording and epithelial transport measurements on taste tissue, we will determine the basic electrophysiology of fungiform and circumvallate taste receptor cells. We will also determine the ionic Na transport pathways in these cells in order to elucidate the mechanisms for salt transduction. 2. What are the effects of vasopressin and atrial natriuretic peptide upon the transducing elements for salts? Our recent work showing that vasopressin enhances amiloride-sensitive Na currents in fungiform taste receptor cells coupled with preliminary evidence which demonstrates that atrial natriuretic peptide reduces transepithelial Na flux, suggests that peripheral Na salt transduction may be hormonally regulated. We will characterize the acute and chronic effects of vasopressin and atrial natriuretic peptide upon transepithelial Na transport and Na transducing channels at the whole cell and single channel level, paying particular attention to the amiloride-sensitive Na channel. We will then determine the targets and the pathways involved in the cellular response to these two hormones. Overall, these studies will elucidate basic electrophysiological properties of taste receptor cells and mechanisms for Na salt transduction in the hamster. Additionally, it will, for the first time, look at the role of hormones in the regulation and modulation of peripheral gustatory responsiveness. These studies will enhance understanding of nutrient chemoreception and its regulation as well as provide general insights into how neurons transduce sensory stimuli.