VIP RECEPTORS AND SUBMANDIBULAR GLAND FUNCTION

唾液腺的正常功能对口腔健康至关重要。 在 近年来，已知的激素和神经递质的数量 在调节唾液腺功能中的重要生理作用， 明显增加。 随着这一增长， 影响唾液过程的各种疾病状态可能涉及一种或多种 这些化合物。 其中一个主要的例子是“新”代理， 与腺体功能密切相关的是血管活性肠肽 （VIP）。 这28个氨基酸的肽是代理的主要候选人 引起了在下颌下腺中观察到的阿托品抵抗性血管舒张， 几个物种。 实验证据表明，VIP的其他功能， 唾液腺 拟议的研究的目的是表征细胞表面 大鼠下颌下腺VIP受体的研究 第二个目标是 探索不同神经递质受体的相互作用， 它们对受体亲和力和密度的交叉调节。 我们 实现这些目标的方法首先包括研究 血管活性肠肽及相关肽在大鼠离体颌下腺灌注中的表达 血流、唾液分泌、唾液电解质和蛋白质 内容 第二，我们将检查分离的腺泡细胞的肽效应 离子流 第三，将对这些相同的制剂进行分析， 细胞内信使对VIP的反应性。 最后，我们将使用 放射性配体结合研究，以（1）将这些功能研究与 VIP与其受体的相互作用;（2）研究VIP与其受体的相互作用， 受体串扰 结肠来源的HT 29细胞系具有许多属性，使其成为 一个有用的模型系统，用于研究上述许多过程，并将 在我们研究VIP对下颌下腺的作用时， 功能 这些目标的实现将提供一个更全面的 了解正常的唾液功能，并提出新的途径， 研究影响外分泌腺的疾病状态。

Proper functioning of the salivary glands is essential to oral health. In recent years the number of hormones and neurotransmitters known to have important physiological roles in regulating salivary gland function has markedly increased. With this increase has come an appreciation that various disease states affecting salivary processes may involve one or more of these compounds. One of the primary examples of "new" agents that are intimately involved in gland function is vasoactive intestinal peptide (VIP). This 28 amino acid peptide is the primary candidate for the agent causing the atropine-resistant vasodilation seen in submandibular glands of several species. Experimental evidence suggests other functions of VIP in salivary glands. The objective of the proposed research is to characterize the cell surface receptors for VIP in rat submandibular gland. A second objective is to explore the interaction of receptors for distinct neurotransmitters in terms of their crossmodulation of receptor affinity and density. Our approach to these objectives will involve first, studies of the effects of VIP and related peptides in isolated, perfused submandibular glands in terms of blood flow, salivary secretion and saliva electrolyte and protein content. Second, we will examine isolated acinar cells for peptide effects on ion fluxes. Third, these same preparations will be assayed for responsiveness of intracellular messengers to VIP. Finally, we will use radioligand binding studies to (1) correlate these functional studies with the interaction of VIP and its receptor and (2) examine the phenomenon of receptor cross-talk. The HT29 cell line of colonic origin has many attributes that make it a useful model system for studying many of the above processes and will be used secondarily in our studies of VIP effects on submandibular gland function. Attainment of these objectives will provide a fuller understanding of normal salivary function and suggest new avenues of investigation in disease states affecting exocrine glands.