Mechanism underlying streptozotocin-induced xerostomia and curative drug

链脲佐菌素引起口干症的机制及治疗药物

• 批准号: 13470393
• 负责人: ISHIKAWA Yasuko
• 金额: $ 9.22万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470393/
• 关键词: Water channel; Aquaporin-5; Salivary glands; Diabetes; Xerostomia; Lipid rafts; Apical membrane; Cevimeline; SNI-2011; アクアポリン-5; アクアポリン-8; M3ムスカリン受容体; 唾液分泌不全; チアゾリジン系薬物

Parotid secretory response to the activation of M3-muscarinic acetylcholine receptors (mAChRs) is reduced in streptozotocin.-induced diabetic (STZ) rats. In this research eve investigated the mechanisms involved in the decreased secretory response in coupled with the alteration of the distribution of aquaporin-5 (AQP5) water channel. Parotid slices from Wister rats gived STZ were incubated with or without mAChR agonists or other agents. Cevimeline hydrochloride (SNI-2011) increased AQPS levels in apical plasma membrane by 3-fold in parotid glands in normal rats, but by 0.8-fold in those of STZ rats. SNI-2011 increases AQP5 levels in basolateral membrane in STZ rats. Although mRNA of AQP5 was increased, the amount of AQP5 in parotid homogenate or lipid rafts was decreased in STZ rats. Both the quantities and affinity of mAChRs were decreased, but the amount of Gq proteins were not changed in STZ rats compared with ncontrol rats. In conclusion, mAChR agonists did not induce the increase in the amount of AQP5 in the apical plasma membrane of parotid glands from STZ rats because of the ~~ defect of translocation of AQP5 from rafts to the apical plasma membrane

腮腺对M3-毒蕈碱乙酰胆碱受体（mAChR）激活的分泌反应在链脲佐菌素中减少。诱导糖尿病（STZ）大鼠。本研究探讨了水通道蛋白5（AQP 5）分布改变与分泌反应降低的相关机制。给予STZ的Wister大鼠的腮腺切片与或不与mAChR激动剂或其他试剂一起孵育。盐酸头孢美林（SNI-2011）使正常大鼠腮腺顶端质膜AQPS水平增加3倍，但STZ大鼠增加0.8倍。SNI-2011增加STZ大鼠基底外侧膜中的AQP 5水平。STZ组大鼠腮腺组织匀浆及脂筏中AQP 5 mRNA表达增加，但AQP 5含量减少。与对照组相比，STZ组大鼠mAChRs的数量和亲和力均降低，而Gq蛋白的数量无明显变化。总之，mAChR激动剂不能诱导STZ大鼠腮腺顶质膜AQP 5的增加，这是由于AQP 5从筏到顶质膜的转位存在缺陷

项目成果

Yasuko Ishikawa: "Activation of endogenous nitric oxide synthase coupled with methacholine-induced exocytosis in rat parotid acinar cells"J. Pharmacol. Exp. Ther.. Vol.301 No.1. 1-9 (2002)

Yasuko Ishikawa：“内源性一氧化氮合酶的激活与乙酰甲胆碱诱导的大鼠腮腺腺泡细胞的胞吐作用相结合”J。

井上紀子: "糖尿病と唾液腺分泌機能の変化"歯科基礎医学会雑誌. Vol.43, No.5. 588 (2001)

井上纪子：“糖尿病和唾液腺分泌功能的变化”日本基础牙科医学会杂志第43卷，第588期（2001年）。

Yasuko Ishikawa: "「Molecular biology and physiology of water and solute transport」 Edited by Stefan"Kluwer Academic/Plenum Publishers, London, UK. 451 (2001)

Yasuko Ishikawa：“水和溶质运输的分子生物学和生理学”，Stefan 编辑”Kluwer Academy/Plenum Publishers，伦敦，英国。451（2001）

Yasuko Ishikawa: "Neurotransmitters regulate amount of AQP5 in apical membrane of parotid"Journal Dental Research. Vol.80. 600 (2001)

Yasuko Ishikawa：“神经递质调节腮腺顶膜中 AQP5 的量”《牙科研究杂志》。

Noriko Inoue: "SNI-2011-induced persistent increase in the amount of AQP5 in APM"Journal Dental Research. Vol.80. 676 (2001)

Noriko Inoue：“SNI-2011 诱导 APM 中 AQP5 数量持续增加”《牙科研究杂志》。