Watanabe M, Yamagishi-Wang H, Kawaguchi M
Department of Pharmacology, Tokyo Dental College, Chiba, Japan.
Jpn J Pharmacol. 2001 Oct;87(2):117-24. doi: 10.1254/jjp.87.117.
We investigated the responses of salivary secretion and the susceptibility of the muscarinic receptors in the salivary glands of the streptozotocin (STZ)-induced diabetic rats (STZ rats). Giving water ad libitum, the amount of whole saliva with no stimulation was similar in the STZ and the control rats. Pilocarpine increased salivary secretion in both groups, although the effect in the STZ rats was two to three fold less than in the control rats. If the animals were restricted from taking water for 6 h, salivary secretion was not slightly changed in the STZ rats in spite of a remarkable increase in the control. An obvious decrease in salivary secretion of the STZ rats was negatively correlated with an increase in urination. Furthermore, salivary secretion from the parotid gland was increased in a dose-dependent manner with pilocarpine in the control rats, but not in the STZ rats. In the [3H]quinuclidinyl benzilate (QNB) binding studies for muscarinic receptor of the STZ rats, Bmax was decreased in the parotid gland and Kd was increased in the submandibular gland. Competitive inhibition of [3H]QNB binding to both glands showed an increase in IC50 of pilocarpine and carbachol. These results suggest that a decrease in salivary secretion of STZ rats is not only induced by a water loss, but also closely associated with the lowered susceptibility of the muscarinic receptors.
我们研究了链脲佐菌素（STZ）诱导的糖尿病大鼠（STZ大鼠）唾液腺中唾液分泌的反应以及毒蕈碱受体的敏感性。随意饮水时，STZ大鼠和对照大鼠无刺激情况下的全唾液量相似。毛果芸香碱可增加两组的唾液分泌，尽管STZ大鼠的效果比对照大鼠低两到三倍。如果动物被限制饮水6小时，尽管对照大鼠唾液分泌显著增加，但STZ大鼠的唾液分泌没有轻微变化。STZ大鼠唾液分泌的明显减少与尿量增加呈负相关。此外，在对照大鼠中，腮腺的唾液分泌随毛果芸香碱呈剂量依赖性增加，但在STZ大鼠中则不然。在对STZ大鼠毒蕈碱受体的[3H]喹核醇基苯甲酸酯（QNB）结合研究中，腮腺中的Bmax降低，颌下腺中的Kd增加。对两个腺体[3H]QNB结合的竞争性抑制显示毛果芸香碱和卡巴胆碱的IC50增加。这些结果表明，STZ大鼠唾液分泌的减少不仅是由水分流失引起的，而且与毒蕈碱受体敏感性降低密切相关。
