VIP RECEPTORS AND SUBMANDIBULAR GLAND FUNCTION

唾液腺的正常运作对口腔健康至关重要。在……里面 近年来，已知的激素和神经递质的数量 在调节唾液腺功能方面具有重要的生理作用 明显增加。随之而来的是一种升值，即 影响唾液过程的各种疾病状态可能涉及一种或多种 这些化合物中。“新”代理的主要例子之一就是 与腺体功能密切相关的是血管活性肠肽 (VIP)。这种28个氨基酸的多肽是该试剂的主要候选者。 引起颌下腺出现阿托品抵抗的血管扩张 几个物种。实验证据表明VIP在脑内的其他功能 唾液腺。 拟议研究的目标是确定细胞表面的特征。 大鼠颌下腺的血管活性肠肽受体。第二个目标是 探讨不同神经递质受体之间的相互作用 它们对受体亲和力和密度的交叉调节。我们的 实现这些目标的方法将首先涉及对以下方面影响的研究 血管活性肠肽及其相关多肽在大鼠离体颌下腺中的表达 血流量、唾液分泌物、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多肽效应。 关于离子通量。第三，将对这些相同的制剂进行检测 细胞内信使对VIP的反应性。最后，我们将使用 放射性配基结合研究：(1)将这些功能研究与 血管活性肠肽与其受体的相互作用及(2)研究血管活性肠肽与其受体的相互作用 接收器串扰。 结肠起源的HT29细胞系具有许多属性，使其成为 用于研究上述许多过程的有用的模型系统，并将 二次用于VIP对颌下腺影响的研究 功能。实现这些目标将提供更全面的 对正常唾液功能的了解并提出新的治疗途径 对影响外分泌腺的疾病状态进行调查。

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.