Relationship between proteins related to exocytosis regulation in salivary glands

在唾液腺中，β-肾上腺素能和毒蕈碱胆碱能受体的刺激引起蛋白质的胞吐分泌。细胞内cAMP水平和Ca ~（2+）浓度分别通过β-肾上腺素能受体和毒蕈碱胆碱能受体的激活而增加，它们作为细胞信号发挥作用。我们研究了唾液腺中与胞吐调控相关的蛋白质与其细胞信号的关系，并展示了几个结果。1建立了大鼠腮腺腺泡细胞原代培养体系，该体系保持了β-肾上腺素能受体和毒蕈碱胆碱能受体激活引起的调节性胞吐功能。（2）证实了大鼠腮腺分泌颗粒中存在水通道蛋白-5（aquaporin-5），提示该通道参与了与Cl-转运有关的颗粒膜调节。（3）在家兔下颌下腺中，一氧化氮合酶的活性受磷脂酰肌醇4，5-二磷酸和磷脂酸的调节。4）证实环核苷酸磷酸二酯酶1和2参与了毒蕈碱受体激活诱导的兔下颌下腺细胞cGMP水平的调节。5）在兔腮腺腺泡细胞中发现两种Ca ~（2+）/钙调素依赖的环核苷酸磷酸二酯酶，它们可被M受体激活引起的Ca ~（2+）水平升高所激活。6）提出了分泌颗粒膜结构域（抗洗涤剂膜结构域）的变化与syntaxin 6的关系，认为syntaxin 6与分泌颗粒的成熟有关。我们认为这些结果是唾液腺功能的新信息。

In salivary glands, stimulation of β-adrenergic and muscarinic cholinergic receptors provokes exocytotic secretion of proteins. Cellular cAMP level and intracellular Ca2+ concentration are increased by activation of β-adrenergic and muscarinic cholinergic receptors, respectively, and they play as cellular signals. We investigated relationship between proteins related to exocytosis regulation and its cell signaling in salivary glands, and demonstrated several results. 1 We established a primary culture system of rat parotid acinar cells, which kept regulatory exocytotic functions provoked by β-adrenergic and muscarinic cholinergic receptor activation. 2)We confirmed the presence of aquaporirn-5 water channels in secretory granules of the rat parotid gland, and suggested that the water channels are involved in granule osmoregulation related to Cl- transport. 3)We demonstrated that the activity of nitric oxide synthase, which is activated by muscarinic receptor activation via increase in intracellular Ca2+, was regulated by phospholipids such as phosphatidyl inositol 4,5-bisphosphate and phosphachidic acid in the rabbit submandibular gland. 4)We demonstrated that cyclic nucleotide phosphodiesterases 1 and 2 were involved in the regulation of cellular cGMP level induced by muscarinic receptor activation in rabbit submandibular gland cells. 5)We found that two kinds of Ca2+/calmodulin-dependent cyclic nucleotide phosphodiesterase, which were activated by Ca2+ levels induced by muscarinic receptor activation, in rabbit parotid acinar cells. 6)We suggested the relationship between changes of membrane domain (detergent-resistant membrane domains) and syntaxin 6, which is considered to be related to maturation of secretory granules. We believe that these results are new information on salivary gland function.