PILOCARPINE INHIBITION OF GAMMA-GLUTAMYLTRANSPEPTIDASE

谷氨酰转肽酶(GGT)是一种与细胞表面相关的 存在于细胞中的具有分泌或吸收功能的酶。 提高GGT的产量和/或GGT的大幅增加 活动性可作为发现癌前病变的标志 口腔。GGT活性的表达与调控 在正常和肿瘤的发育过程中， 发展对正在发生的综合事件的理解 在正常和异常生长期间。最近，匹罗卡品 研究表明，给药会导致GGT显著下降 颌下腺的腺泡细胞活动。由此 有报道认为匹罗卡品的抑制作用为 通过直接影响酶来调节。我们相信 该报告的作者对数据的解释是错误的。 由于匹罗卡品已知通过以下途径调节其其他作用 胆碱能受体的刺激，我们认为观察到的 抑制可以用富含GGT的膜的丧失来解释 分泌物和膜中的片段或GGT失活 回收利用。我们建议通过研究其影响来研究这一点。 匹罗卡品：对非靶器官(肾脏)GGT活性的影响 纯化的GGT酶制剂及其匀浆(酶) 动力学)；在另一种表面结合酶(碱性 磷酸酶)。此外，我们还将直接观察GGT和 对照和匹罗卡品处理后组织中GGT活性的变化 组织化学和免疫组织化学技术。平行 将进行超微结构研究，以改善 上述技术的解决方案。

Gamma-glutamyltranspeptidase (GGT) is a cell surface associated enzyme found in cells having secretory or absorptive functions. Enhanced production of GGT and/or a dramatic increase in GGT activity can be a hallmark for detecting preneoplastic lesions of the oral cavity. The expression and regulation of GGT activity during normal and neoplastic development is important in developing an understanding of the synthetic events occurring during normal and abnormal growth. Recently, pilocarpine administration was shown to cause a significant drop in GGT activity in the acinar cells of the submandibular gland. From this report was suggested that the inhibitory effect of pilocarpine was mediated by directly affecting the enzyme. We believe the interpretation of the data by the authors of that report is in error. Since pilocarpine is known to mediate its other effects by stimulation of cholinergic receptors, we think the observed inhibition could be explained by the loss of GGT-rich membrane fragments or GGT inactivation during secretion and membrane recycling. We propose to investigate this by studying the effect of pilocarpine: on GGT activity in a non-target organ (kidney); on a purified GGT enzyme preparation and homogenate (enzyme kinetics); on another surface associated enzyme (alkaline phosphatase). Furthermore, we will directly observe GGT and GGT activity in control and pilocarpine-treated tissue by histochemical and immunohistochemical techniques. Parallel ultrastructural studies will be undertaken to improve the resolution of the above techniques.