Acetylcholine-evoked calcium mobilization and ion channel activation in human labial gland acinar cells from patients with primary Sjogren's syndrome
Acetylcholine-evoked calcium mobilization and ion channel activation in human labial gland acinar cells from patients with primary Sjogren's syndrome
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DOI：
10.1046/j.1365-2249.2001.01526.x
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发表时间：
2001-06-01
影响因子：
4.6
通讯作者：
Smith, PM
中科院分区：
文献类型：
--
作者：
Dawson, LJ;Field, EA;Smith, PM
最近的证据表明，与干燥综合征(SjS)相关的唾液腺功能障碍并不一定是由于免疫介导的腺泡组织破坏。SJS患者可能拥有大量的腺泡组织储备，但仍无法将唾液流率维持在正常范围。我们用Fura-2微量荧光法测定激动剂引起的细胞内钙离子([Ca~(2+)](I))的变化，并用膜片钳全细胞技术检测K~+和Cl~-通道的激活，研究SjS患者唇腺腺泡细胞分泌液体的能力。我们可以证实，超大剂量的乙酰胆碱(ACh)刺激使对照组和SjS患者来源的腺泡细胞的[Ca~(2+)](I)水平均升高。然而，在次最大浓度下，SjS患者的腺泡细胞ACh的剂量-反应曲线与对照组相比右移了大约一个数量级。从对照腺泡细胞和SjS患者获得的膜片钳测量结果与存在钙激活的K+和Cl-电导一致。在SjS患者的腺泡细胞中，乙酰胆碱对离子通道的剂量依赖性激活也比对照细胞右移。我们的数据表明，SjS患者的唇腺腺泡细胞能够对激动剂刺激作出反应，动员[Ca~(2+)](I)，激活与液体分泌要求一致的K~+和Cl~-通道。然而，在SjS患者体内观察到的对ACh的持续敏感性丧失可能是这些患者体内观察到的唾液产生不足的原因。
Recent evidence has indicated that the salivary gland dysfunction associated with Sjogren's syndrome (SjS) is not necessarily due to immune-mediated destruction of acinar tissue. SjS sufferers may possess substantial reserves of acinar tissue but nevertheless be incapable of maintaining salivary flow rates in the normal range. We have investigated the ability of isolated labial gland acinar cells from SjS patients to fluid secrete by measuring agonist-evoked changes in intracellular Ca2+ ([Ca2+](i)) using fura-2 microfluorimetry and activation of K+ and Cl- channels using the patch-clamp whole cell technique. We can confirm that stimulation with a super-maximal dose of acetylcholine (ACh) increased [Ca2+](i) equally in both control acinar cells and those derived from SjS patients. However, at submaximal concentrations, the dose-response curve for ACh was shifted to the right by approximately one order of magnitude in acinar cells from SjS patients compared to control acinar cells. Patch-clamp measurements consistent with the presence of Ca2+-activated K+ and Cl- conductances were obtained from both control acinar cells and those obtained from SjS patients. Dose-dependent activation of the ion channels by acetylcholine was also right-shifted in acinar cells from SjS patients compared to control cells. Our data show that labial gland acinar cells from SjS patients were capable of responding to agonist stimulation by mobilizing [Ca2+](i) and activating K+ and Cl- channels consistent with the requirements of fluid secretion. However, the persistent loss of sensitivity to ACh observed in from SjS patients may account for the lack of saliva production observed in these patients in vivo.