Diquafosol elicits increases in net Cl- transport through P2Y2 receptor stimulation in rabbit conjunctiva
Diquafosol elicits increases in net Cl- transport through P2Y2 receptor stimulation in rabbit conjunctiva
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DOI：
10.1159/000076887
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发表时间：
2004-01-01
影响因子：
2.1
通讯作者：
Nakamura, M
中科院分区：
文献类型：
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作者：
Murakami, T;Fujihara, T;Nakamura, M
本研究的目的是了解地夸磷索（一种稳定的尿苷5 '-三磷酸衍生物）对离体兔结膜Cl-转运的作用机制。分离兔结膜并固定在改良的Ussing室中。在短路条件下，测定粘膜（泪液）侧地夸磷索应用对短路电流（Isc）的影响。当加入到结膜的粘膜侧时，地夸磷索在0.1至968 μ M的浓度范围内快速且剂量依赖性地增加了Isc。在不存在丝氨酸Cl-的情况下，由10 μ M地夸磷索诱导的Isc显著降低。相反，在不存在粘膜侧Na+的情况下，地夸磷索诱导的Isc增加不变。预孵育45分钟后，P2 Y（2）拮抗剂苏拉明抑制地夸磷索诱导的Isc增加，而P2 Y（1）拮抗剂磷酸吡哆醛-6-偶氮苯基-2 '4 '-二磺酸则无影响。这些研究表明，地夸磷索通过刺激兔结膜中的P2 Y2受体，刺激从浆膜到粘膜侧的净Cl-分泌。版权所有（C）2004 S. Karger AG，巴塞尔。
The purpose of the present study was to understand the mechanisms of action of diquafosol, a stable derivative of uridine 5'-triphosphate, on Cl- transport across the isolated rabbit conjunctiva. Rabbit conjunctivas were isolated and mounted in a modified Ussing chamber. Under short-circuit conditions, the effects were determined of mucosal (tear) side diquafosol application on the short-circuit current (Isc). Diquafosol rapidly and dose-dependently increased the Isc at concentrations ranging from 0.1 to 968 muM when added to the mucosal side of the conjunctiva. In the absence of the serosal Cl-, the Isc induced by 10 muM diquafosol was substantially reduced. On the contrary, in the absence of mucosal side Na+, the diquafosol-induced increases in Isc were unchanged. Following 45-min preincubation, the P2Y(2) antagonist suramin inhibited the diquafosol-induced increases in the Isc whereas the P2Y(1) antagonist pyridoxal-phosphate-6-azophenyl-2'4'-disulfonic acid had no effect. These studies suggest that diquafosol stimulates net Cl- secretion from the serosal to the mucosal side via stimulation of P2Y2 receptors in the rabbit conjunctiva. Copyright (C) 2004 S. Karger AG, Basel.