Mechanism underlying streptozotocin-induced xerostomia and curative drug

链脲佐菌素诱导的糖尿病(STZ)大鼠腮腺对M3-M胆碱受体(MAChRs)激活的分泌反应降低。本研究探讨了水通道蛋白-5(AQP5)水通道分布的改变和分泌反应降低的机制。给予STZ的Wister大鼠的腮腺切片与或不与mAChR激动剂或其他药物孵育。盐酸西维米林(SNI-2011)使正常大鼠腮腺顶端质膜AQPs水平增加3倍，而STZ大鼠则增加0.8倍。SNI-2011增加STZ大鼠基底膜AQP5水平。STZ大鼠腮腺组织匀浆或脂筏中AQP5的表达虽然增加，但AQP5的表达减少。与正常对照组相比，STZ大鼠的mAChRs数量和亲和力均降低，但Gq蛋白的数量无明显变化。结论：mAChR激动剂不能诱导STZ大鼠腮腺顶端质膜AQP5的数量增加，这是因为AQP5从筏到顶端质膜的移位存在缺陷。

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