VIP RECEPTORS AND SUBMANDIBULAR GLAND FUNCTION

血管活性肠肽（VIP）是一种 神经支配哺乳动物下颌下腺（SMG）， 参与调节唾液的产生和分泌， 这对口腔卫生和消化至关重要。 虽然 血管活性肠肽对血管舒张、唾液容量和离子含量的影响 已经在体内和器官制备物中描述， 离子转运过程受VIP受体活化调节， 实现这一调节的机制是 未知 其他组织中的VIP受体与 腺苷酸环化酶，至少在HT 29结肠细胞中，VIP 受体/腺苷酸环化酶系统被先前的 暴露于受体激动剂或蛋白质激活剂 激酶C SMG中的VIP受体是否在此过程中受到调节 的方式，以及该规定对SMG离子的后果是什么 运输系统未知。 虽然没有一个人 确定，一个连续的，同质的细胞系保留 正常SMG腺泡或导管细胞的特征将非常 对研究SMG离子传输很有用。 因此除了 评估VIP对灌注腺体中离子转运系统的影响 在腺泡中，A-253腺癌细胞系分离自 人颌下腺将作为研究的模型进行评估 SMG离子转运，VIP-R介导的对离子转运的影响， VIP受体的调节。 初步数据显示， 细胞将是有用的，因为A-253细胞表现出VIP 受体/腺苷酸环化酶系统被下调 被Na/K ATP酶阻断的激动剂和离子转运系统 和aa/K/Cl共转运抑制剂。 利用灌注腺体， 腺泡和A-253细胞，SMG功能的三个主要方面 将得到解决。 这些是VIP受体在 调节剂特异性SMG离子转运过程和机制 其中; SMG VIP的同源和异源调节 受体/腺苷酸环化酶系统;和VIP的后果 受体/腺苷酸环化酶调节SMG离子转运。 的 从这些研究中获得的信息有望提供一个 对正常涎腺血管活性肠肽作用的进一步认识 功能，并建立一个框架，在其中研究病变， 神经肽受体/信号系统 唾液腺和其他外分泌腺。

Vasoactive intestinal peptide (VIP) is one of several transmitters innervating mammalian submandibular salivary glands (SMG) and are involved in regulating saliva production and secretion, processes that are essential for proper oral hygiene and digestion. Although effects of VIP on vasodilation and saliva volume and ion content have been described in in vivo and organ preparations, the specific ion transport processes regulated by VIP receptor activation and the mechanisms through which this regulation is accomplished are unknown. VIP receptors in other tissues are positively coupled to adenylate cyclase and, at least in HT29 colon cells, the VIP receptor/adenylate cyclase system is down-regulated by prior exposure to either receptor agonists or activators of protein kinase C. Whether VIP receptors in SMG are regulated in this manner, and what the consequences of this regulation are on SMG ion transport systems are not known. Although none have been identified, a continuous, homogeneous cell line retaining characteristics of normal SMG acinar or ductal cells would be very useful in studying SMG ion transport. Therefore, in addition to assessing VIP effects on ion transport systems in perfused glands and in acini, the A-253 adenocarcinoma cell line isolated from human submaxillary gland will be evaluated as a model for studying SMG ion transport, VIP-R mediated effects on ion transport and regulation of VIP receptors. Preliminary data suggest that these cells will be useful, in that A-253 cells exhibit a VIP receptor/adenylate cyclase system that is down-regulated by agonists and ion transport systems that are blocked by Na/K ATPase and aa/K/Cl cotransport inhibitors. Using perfused glands, isolated acini and A-253 cells, three major aspects of SMG function will be addressed. These are the role of VIP receptors in regulator specific SMG ion transport processes and the mechanisms thereof; the homologous and heterologous regulation of the SMG VIP receptor/adenylate cyclase system; and the consequences of VIP receptor/adenylate cyclase regulation on SMG ion transport. The information obtained from these studies promises to provide a fuller understanding of the role of VIP in normal salivary gland function and to establish a framework in which to study lesions in neuropeptide receptor/signaling systems in diseases affecting salivary and other exocrine glands.