Effects of pilocarpine and cevimeline on Ca2+ mobilization in rat parotid acini and ducts.
Effects of pilocarpine and cevimeline on Ca2+ mobilization in rat parotid acini and ducts.
复制标题
毛果芸香碱和西维美林对大鼠腮腺腺泡和导管中 Ca2+ 动员的影响。
DOI：
10.2152/jmi.56.375
复制
发表时间：
2009
期刊：
影响因子：
--
通讯作者：
K. Inenaga
中科院分区：
文献类型：
--
作者：
K. Ono;T. Inagaki;Taichi Iida;R. Hosokawa;K. Inenaga
先前的报道表明，匹罗卡品和西维米林对毒蕈碱受体的结合亲和力没有显著差异(1)。然而，我们实验室的体内研究表明，在大鼠中，匹罗卡品诱导的腮腺分泌的唾液比西维美林诱导的要多。因此，在本研究中，我们在离体腮腺细胞中研究了涎腺诱导的细胞内Ca（2+）动员。匹洛卡平和西维米林使腮腺腺泡和导管细胞内Ca（2+）浓度在1 μ m以上呈剂量依赖关系。匹洛卡品诱导的反应高于西维美林诱导的反应。Ca（2+）对这两种药物的反应被一种M3毒蕈碱受体拮抗剂1 μ m 4-DAMP完全阻断。在缺乏细胞外Ca（2+）的情况下，两种涎物均诱导腮腺腺泡细胞瞬时Ca（2+）升高。这些结果表明，这些涎物通过Ca（2+）信号刺激腮腺腺泡细胞的一些共同途径。我们还报道了在腮腺腺泡细胞中，皮洛卡平和西维美林浓度的Ca（2+）反应有显著差异。不同的Ca（2+）反应可以解释我们在之前的体内研究中观察到的它们之间腮腺唾液量的不同。
Previous reports suggested that there is no significant difference in the binding affinity of pilocarpine and cevimeline on muscarinic receptors (1). However, in vivo studies from our laboratory suggested that pilocarpine-induced salivation from the parotid gland is greater than that induced by cevimeline in rats. Therefore, in the present study, sialogogue-induced intracellular Ca(2+) mobilization was investigated in isolated parotid gland cells in vitro. Pilocarpine and cevimeline increased the intracellular Ca(2+) concentration of parotid gland acinar and duct cells over 1 microM in a dose-dependent manner. Pilocarpine-induced responses were higher than cevimeline-induced responses. Ca(2+) responses to both agents were completely blocked by 1 microM 4-DAMP, an M3 muscarinic receptor antagonist. In the absence of extracellular Ca(2+), both sialogogues induced transient Ca(2+) increase in parotid gland acinar cells. These results suggest that the sialogogues stimulate some common routes via the Ca(2+) signaling in parotid gland acinar cells. We also report a significant difference of Ca(2+) responses in concentration between pilocarpine and cevimeline in parotid gland acinar cells. The different Ca(2+) responses between the sialogogues would explain the different saliva volumes from the parotid gland between them that we have observed in previous in vivo studies.