A study of mechanisms underlying M3 muscarinic agonist-induced trafficking of AQP5 to nuclei, functions of AQP5 located in nuclear membrane and a development of a drug for age-dependent xerostomia

M3毒毒碱乙酰胆碱受体（mAChR）或α 1肾上腺素受体的激活可引起大鼠腮腺核膜和顶质膜水通道蛋白-5 （AQP）的增加。我们研究了西维米林（mAChR激动剂）诱导AQP5转运到细胞核的机制。注射西维美林后3 min核膜内检测到AQP5和Rab5的共免疫沉淀。我们观察了在西维美林作用下腮腺核中AQP5和Rab5的分布。注射西维美林后3min， 1% Triton x溶性和不溶性核膜组分AQP5升高。核膜AQP5很少在蔗糖密度梯度中漂浮。对照条件下，细胞核直径为5.5微米，西维美林处理后3分钟，细胞核直径降至3.5微米。人工唾液的管理(专利号：2013-022555)阻止了AQP5向细胞核转运的年龄依赖性减少。

Activation of M3 muscarinic acetylcholine receptor (mAChR) or alpha 1 adrenoceeptor induces the increase in the amount of aquaporin-5 (AQP) in nuclear membrane and apical plasma membrane of rat parotid glands. We investigated the mechanisms underlying cevimeline (mAChR agonist)-induced trafficking of AQP5 to nuclei. Co-immunoprecipitation of AQP5 and Rab5 was detected in nuclear membrane 3 min after cevimeline-injection. We visualized the distribution of AQP5 and Rab5 in parotid nuclei in response to cevimeline. AQP5 was increased in 1% Triton X-soluble- and -insoluble-nuclear membrane fractions 3 min after cevimeline-injection. Very few AQP5 of nuclear membrane were floated in sucrose density gradient. Under control conditions, the diameter of nuclei was 5.5 micro m. The diameter was decreased to 3.5 micro m 3 min after cevimeline treatment. Administration of artificial saliva (patent no. 2013-022555) prevented age-dependent decreases of AQP5 trafficking to nuclei.