SALIVARY GLAND SECRETORY MECHANISMS DURING NORMAL AND ALTERED FUNCTIONAL STATES

正常和功能改变状态下的唾液腺分泌机制

• 批准号: 3839193
• 负责人: B J BAUM
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3839193
• 关键词: G protein; acinar cell; alpha adrenergic receptor; anticholinergic agent; biological signal transduction; calcium; cyclic AMP; inositol phosphates; laboratory rat; muscarinic receptor; neurochemistry; neurotransmitters; parotid gland; phospholipase C; quinuclidines; receptor coupling; saliva; second messengers; secretion; tissue /cell culture

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.

口腔的健康是由唾液分泌物维持的。 公关 cipal 唾液腺的功能是产生这些复杂的流体。 我们利用 n体外 分散的唾液腺细胞以了解控制SAL的机制 形成。 我们将研究重点放在分泌前夕的神经递质调节上 沙 相关的信号机制。 在此报告期间 研究 继续是大鼠腮腺腺泡C中的毒蕈碱受体（MACHRS） LS及其 通过特定的G蛋白与功能响应耦合。 我们也有ini ATED研究 这些细胞中的α-肾上腺素能受体（α1-ARS）。 在腮腺细胞中 刺激 MACHRS通过Activati产生肌醇磷酸盐的产生 一个 磷脂酰肌醇4,5-双磷酸特异性磷脂酶C.随后的 这 响应导致胞质Ca2+水平和流体秘密的升高 此外，MACHR可以介导对激动剂诱导的营地的抑制 tion。 我们 已经表征了亚型非选择性拮抗剂的结合（Quinu idinyl 苯甲酸盐，QNB）到完整的大鼠腮腺细胞中的MACHR。 特定的结合是 易于 时间和温度依赖性（BMAX约80 fmol/mg蛋白； kd 近距离 100 pm）。 另外，我们已经评估了MACHR入住a之间的关系 第二 Messenger组成，确定中等人口（大约 -40％） 存在用于肌醇三磷酸盐（IP3）形成的备用受体。 我们previ 斯利报道 那只大鼠腮腺M3-machrs夫妇到两个不同的信号转导G Pro ins。 这 一年，我们确定了编码此RECE区域的核苷酸序列 或基因 参与G蛋白耦合，我们观察到它实际上是相同的 向其他人 报告了3个序列。 因此，MACHR本身不太可能是责任 为了 发散耦合。 此外，我们已经证明了α1-肾上腺素能 Eceptor 与流体分泌反应有关的亚型是α1a。