VIP RECEPTORS AND SUBMANDIBULAR GLAND FUNCTION

血管活性肠肽(VIP)是多种递质之一 支配哺乳动物的颌下腺(SMG) 参与调节唾液的产生和分泌、过程 这对适当的口腔卫生和消化是必不可少的。虽然 血管活性肠肽对血管扩张、唾液体积和离子含量的影响 已经在体内和器官中描述了制剂的具体情况 VIP受体激活和调节的离子转运过程 完成这一监管的机制是 未知。其他组织中的VIP受体与 腺苷环化酶，至少在HT29结肠细胞中，VIP 受体/腺苷环化酶系统受PERE下调 暴露于受体激动剂或蛋白质激活剂 蛋白激酶C：SMG中的VIP受体是否受此调控 方式，以及这一规定对SMG ION的影响 运输系统尚不清楚。尽管没有一个人 鉴定，一个连续的，均一的细胞系保留 正常SMG腺泡或导管细胞的特征是 在研究SMG离子传输方面很有用。因此，除了 血管活性肠肽对腺体离子转运系统的影响 而在腺泡细胞系中，从 人类颌下腺将被评为研究的模型 SMG离子转运、VIP-R介导的离子转运和 VIP受体的调节。初步数据表明，这些 细胞将是有用的，因为A-253细胞表现出VIP 受体/腺苷环化酶系统被下调 Na/K-ATPase阻断的激动剂和离子转运系统 和AA/K/Cl共转运抑制剂。使用灌流腺， 分离的腺泡细胞和A-253细胞是SMG功能的三个主要方面 将会得到解决。这些都是血管活性肠肽受体在 调节剂特异的SMG离子转运过程及其机制 SMG VIP的同源和异源调控 受体/腺苷环化酶系统；血管活性肠病的后果 受体/腺苷环化酶对SMG离子转运的调节。这个 从这些研究中获得的信息承诺提供一个 对VIP在正常唾液腺中作用的更充分认识 功能，并建立一个研究病变的框架 神经肽受体/信号系统在疾病中的作用 唾液和其他外分泌腺。

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.