The role of salivary proteins in taste and feeding

描述（由申请人提供）：苦味感知的变化可能在饮食选择中起关键作用，这对人体健康具有无可争议的影响。虽然苦味化合物通常与有毒物质有关，但大量具有重要营养价值的食物来源含有苦味植物化学物质（例如，西兰花[1]，菠菜[2]），其中许多具有有益价值[1,3]了解苦味是如何被感知和检测的，对于理解饮食选择[4]和提高儿科药物的可接受性[19]非常重要。在正常的喂养和饮用条件下，味觉化合物在到达受体目标之前必须不可避免地与唾液混合，但研究唾液蛋白质如何调节味觉刺激和改变苦味感知的工作很少。唾液中70%的蛋白质组成了一类富含脯氨酸的蛋白质（PRPs）。大鼠的PRP产生是通过饮食暴露于单宁酸而诱导的，单宁酸是包括人类在内的动物经常摄入的一类植物化合物。据推测，PRPs通过与单宁酸结合改变了单宁酸的可接受性，从而降低了单宁酸溶液的感知强度[10,11]。有证据表明，这些蛋白质可能与其他苦味物质有类似的关系。它们在苦味感受器[13]附近产生。PRPs和苦味受体的基因散布在同一条染色体[5]上，最后，基因连锁研究暗示了人类和小鼠中PRPs苦味接受的作用[15-18]。

DESCRIPTION (provided by applicant): Variation in bitter taste perception may play a key role in diet selection, which has an uncontestable effect on human health. Although bitter compounds are often associated with toxic substances a large number of nutritionally significant food sources contain bitter phytochemicals (e.g., broccoli [1], spinach [2]) many of which can have beneficial value [1, 3] Understanding how bitter taste is perceived and detected is of great importance to understanding diet selection [4] and increasing the acceptability of pediatric medicines [19]. Under normal feeding and drinking conditions taste compounds must inescapably mix with saliva before reaching their receptor targets but very little work has been done examining how salivary proteins modulate taste stimuli and alter bitter taste perception. Seventy percent of all salivary proteins make up a class of proteins referred to as proline-rich proteins (PRPs). PRP production is induced in rats by dietary exposure to tannic acid, a class of plant compounds that animals, including humans, regularly consume. It has been hypothesized that PRPs alter the acceptability of tannic acid by binding to tannins and thereby reduce the perceived intensity of the tannic acid solution [10, 11]. There is evidence to suggest that these proteins may have a similar relationship with other bitters. They are produced in close proximity to bitter taste receptors [13]. Genes for PRPs and bitter taste receptors are interspersed on the same chromosome [5] and lastly, gene linkage studies have implicated a role for PRPs bitter acceptance in humans and mice [15-18]. Specific Aim 1 will establish if long term exposure to bitter compounds can increase the expression of PRPs and establish whether oral exposure is necessary and sufficient to cause induction. Saliva will be analyzed for PRP content before and after exposure to diets adulterated with bitter compounds, including quinine and tannic acid. To isolate the site of exposure necessary for PRP induction rats will also be given tannic acid via either oral or gastric exposure. The ability or inability to induce PRP production is not sufficient to predict interactios between the proteins and the bitter tastants. Therefore, Specific Aim 2 will establish if PRP induction can alter the detection threshold for and superthreshold responsiveness to multiple bitter stimuli. Rats will be used to derive psychophysical detection curves of several bitter tastants in the presence and absence of PRPs. Likewise, responsiveness in the suprathreshold range will be assessed in the presence and absence of PRPs with a series of brief-access tests. Collectively, these experiments will test the hypothesis that PRPs alter taste sensitivity for bittr taste stimuli and ultimately blunt unconditioned taste avoidance responses to these compounds. Together these aims could inform methods for increasing the palatability of healthy phytochemicals and pediatric medicines.