SALIVARY GLAND SECRETORY MECHANISMS DURING NORMAL AND ALTERED FUNCTIONAL STATES

口腔的健康是由唾液分泌物维持的。 公关 UNR 唾液腺的功能是产生这些复杂的液体。 我们利用 离体 分散的唾液腺细胞，以了解控制唾液腺的机制， 一个编队。 我们的研究主要集中在神经递质对分泌期细胞的调节上， s和 相关的信号机制。 在本报告所述期间， 研究领域 在大鼠腮腺腺泡细胞中， ls及其 通过特定的G蛋白偶联到功能反应。 我们也有ini 过时的研究 肾上腺素能受体（alpha 1-ARs）的表达。 腮腺细胞 刺激 mAChRs的激活导致肌醇磷酸的产生， 的 磷脂酰肌醇4，5-二磷酸特异性磷脂酶C。 后续 这 反应导致细胞内Ca 2+水平升高和体液分泌增加， 此外，mAChR可介导激动剂诱导的cAMP的抑制， 是的。 我们 已经表征了亚型非选择性拮抗剂（quinu 烷基 二苯甲酸酯，QNB）与完整大鼠腮腺细胞中的mAChR。 特异性结合 可饱和的， 时间和温度依赖性（Bmax约80 fmol/mg蛋白; Kd 近似 100 pM）。 此外，我们还评估了mAChR占用率与 二 信使的形成，决定了适度的人口（大约 -40%） 存在用于三磷酸肌醇（IP 3）形成备用受体。 我们的团队 sly报道 大鼠腮腺M3-mAChR与两种不同信号转导G蛋白偶联 ins. 这 2004年，我们确定了编码该区域的核苷酸序列， 或基因 参与G蛋白偶联，我们观察到它实际上是 到其他 报道了3个序列。 因此，mAChR本身不太可能负责。 为 发散耦合 此外，我们已经表明，α 1-肾上腺素能 受体 参与液体分泌反应的亚型是α 1A。

The health of the oral cavity is maintained by salivary secretions. The pr cipal function of salivary glands is to produce these complex fluids. We utilize n vitro dispersed cells of salivary glands to understand mechanisms controlling sal a formation. We have focused our studies on neurotransmitter regulation of secretory eve s and associated signalling mechanisms. During this reporting period the primary ocus of study continues to be muscarinic receptors (mAChRs) in rat parotid gland acinar c ls and their coupling to functional responses via specific G proteins. We have also ini ated studies of alpha-adrenergic receptors (alpha1-ARs) in these cells. In parotid cell stimulation of mAChRs results in the generation of inositol phosphates via the activati of a phosphatidylinositol 4,5-bisphosphate specific phospholipase C. Subsequent this response leads to the elevation of cytosolic Ca2+ levels and fluid secretio Additionally, mAChRs can mediate the inhibition of agonist induced cAMP for tion. We have characterized the binding of a subtype non-selective antagonist (quinu idinyl benzilate, QNB) to mAChRs in intact rat parotid cells. Specific binding is aturable, time- and temperature-dependent (Bmax approximately 80 fmol/mg protein; Kd proximately 100 pM). Also, we have assessed the relationship between mAChR occupancy a second messenger formation, determining that a moderate population (approximately -40%) of spare receptors exist for inositol trisphosphate (IP3) formation. We previ sly reported that rat parotid M3-mAChRs couple to two different signal transducing G pro ins. This year we determined the nucleotide sequence encoding the region of this rece or gene involved in G-protein coupling and we observed that it is virtually identic to other reported 3 sequences. Thus, the mAChR itself is unlikely to be responsibl for the divergent coupling. Additionally, we have shown that the alpha1-adrenergic eceptor subtype involved in the fluid secretory response is alpha1A.